Pneumonia

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Treatment of community-acquired pneumonia in adults who require hospitalization

Author: Thomas M File, Jr, MD
Section Editors: John G Bartlett, MD, Julio A Ramirez, MD, FACP
Deputy Editor: Sheila Bond, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2019. | This topic last updated: Mar 05, 2019.
INTRODUCTION
Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinguished from
hospital-acquired (nosocomial) pneumonia (HAP).
CAP is a common and potentially serious illness [1-5]. It is associated with considerable morbidity and mortality, particularly in older adult patients and those with significant comorbidities. (See
"Prognosis of community-acquired pneumonia in adults".)
The treatment of CAP in adults who require hospitalization will be reviewed here. A variety of other important issues related to CAP are discussed separately:
● (See "Diagnostic approach to community-acquired pneumonia in adults".)

● (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care".)
● (See "Treatment of community-acquired pneumonia in adults in the outpatient setting".)
● (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults".)
Pneumonia in special populations, such as aspiration pneumonia, immunocompromised patients, HAP, and ventilator-associated pneumonia (VAP) are also discussed separately. (See
"Aspiration pneumonia in adults" and "Pulmonary infections in immunocompromised patients" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)
MANAGEMENT OF HEALTH CARE-ASSOCIATED PNEUMONIA
Health care-associated pneumonia (HCAP) was included in prior hospital-acquired pneumonia (HAP) guidelines [6] (but not current HAP guidelines [7]) to identify patients thought to be at
increased risk for multidrug-resistant (MDR) pathogens coming from community settings. HCAP referred to pneumonia acquired in health care facilities such as nursing homes, hemodialysis
centers, and outpatient clinics or during a hospitalization within the past three months. The rationale for the separate designation of HCAP (and its association with HAP) was that patients with
HCAP were thought to be at higher risk for MDR organisms. However, several studies have shown that many patients defined as having HCAP are not at high risk for MDR pathogens [8-10]
and that this designation is not a good predictor of who will have an infection with an MDR organism [11]. Furthermore, although interaction with the health care system is potentially a risk for
MDR pathogens, underlying patient characteristics (recent receipt of antimicrobials, comorbidities, functional status, and severity of illness) are important independent determinants of risk for
MDR pathogens. In addition, there is no evidence to indicate that treating patients with HCAP according to the recommendations in HAP guidelines improves outcomes [12]. We feel that
patients previously classified as having HCAP should be managed in a similar way to those with CAP (assessing risks for MDR organisms) because patients with HCAP frequently present from
the community and are initially cared for in emergency departments.
DETERMINING THE APPROPRIATE SITE OF CARE
Determining whether a patient with CAP can be safely treated as an outpatient or requires admission to an observation unit, general medical ward, or higher acuity level of inpatient care, such
as an intensive care unit, is an essential first step (algorithm 1). Severity of illness is the most critical factor in making this determination, but other factors should also be taken into account. The
approach to site of care is discussed in greater detail elsewhere. (See "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care", section on
'Approach to site of care'.)
LIKELY PATHOGENS
Although a variety of bacterial pathogens can cause CAP, a limited number are responsible for the majority of cases; in addition, the causative organism is not identified in an appreciable
proportion of patients (table 1 and table 2). (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology'.)
Medical ward — In patients who require hospitalization but not admission to an intensive care unit (ICU), the most frequently isolated pathogens are Streptococcus pneumoniae, respiratory
viruses (eg, influenza, parainfluenza, respiratory syncytial virus, rhinovirus), and, less often, Mycoplasma pneumoniae, Haemophilus influenzae, and Legionella spp (table 2).
Intensive care unit — The distribution is different in patients with CAP who require admission to an ICU. S. pneumoniae is most common, but Legionella, gram-negative bacilli,
Staphylococcus aureus, and influenza are also important (table 2). Community-associated methicillin-resistant S. aureus (MRSA) typically produces a necrotizing pneumonia with high morbidity
and mortality. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'S. aureus'.)
Risk factors for Pseudomonas or drug-resistant pathogens
Gram-negative bacilli (including Pseudomonas) — Risk factors for CAP due to gram-negative bacilli include previous antibiotic therapy, recent hospitalization, immunosuppression,
pulmonary comorbidity (eg, cystic fibrosis, bronchiectasis, or repeated exacerbations of chronic obstructive pulmonary disease that require frequent glucocorticoid and/or antibiotic use),
probable aspiration, and the presence of multiple medical comorbidities (eg, diabetes mellitus, alcoholism) (table 3) [2,13-17]. In a multinational prospective cohort study evaluating 3193
patients hospitalized with CAP at 22 different sites, Pseudomonas aeruginosa was identified as a cause of CAP in 4.2 percent of all cases [17]. Pseudomonal isolates were drug resistant in
approximately half of cases. Independent risk factors for P. aeruginosa infection included prior Pseudomonas infection/colonization (odds ratio [OR] 16.10, 95% CI 9.48-27.35), tracheostomy
(OR 6.50, 95% CI 2.61-16.19), bronchiectasis (OR 2.88, 95% CI 1.65-5.05), need for respiratory or vasopressor support (OR 2.33, 95% CI 1.44-3.78), and very severe COPD (OR 2.76, 95%
CI 1.25-6.06). The prevalence of pseudomonal CAP among patients with prior Pseudomonas infection/colonization and at least one other risk factor was 67 percent. (See "Epidemiology,
pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Gram-negative bacilli' and "Pseudomonas aeruginosa pneumonia".)
Methicillin-resistant Staphylococcus aureus — Risk factors for MRSA include gram-positive cocci in clusters seen on sputum Gram stain, known colonization with MRSA, risk factors for
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colonization with MRSA (eg, end-stage renal disease, contact sport participants, injection drug users, those living in crowded conditions, men who have sex with men, prisoners), recent
influenza-like illness, antimicrobial therapy (particularly with a fluoroquinolone) in the prior three months, necrotizing or cavitary pneumonia, and presence of empyema (table 3).
Streptococcus pneumoniae — Risk factors for drug-resistant S. pneumoniae in adults include:
● Age >65 years

● Beta-lactam, macrolide, or fluoroquinolone therapy within the past three to six months
● Alcoholism
● Medical comorbidities
● Immunosuppressive illness or therapy
● Exposure to a child in a daycare center
Another risk factor is prior exposure to the health care setting such as from prior hospitalization or from residence in a long-term care facility.
Recent therapy or a repeated course of therapy with beta-lactams, macrolides, or fluoroquinolones are risk factors for pneumococcal resistance to the same class of antibiotic [18]. Thus, an
antimicrobial agent from an alternative class is preferred for a patient who has recently received one of these agents.
The impact of discordant drug therapy, which refers to treatment of an infection with an antimicrobial agent to which the causative organism has demonstrated in vitro resistance, appears to
vary with antibiotic class and possibly with specific agents within a class. Most studies have been performed in patients with S. pneumoniae infection and suggest that current levels of beta-
lactam resistance generally do not cause treatment failure when appropriate agents (eg, amoxicillin, ceftriaxone, cefotaxime) and doses are used [19-23]. Cefuroxime is a possible exception
with beta-lactams, and there appears to be an increased risk of macrolide failure in patients with macrolide-resistant S. pneumoniae.
DIAGNOSTIC TESTING
The approach to diagnostic testing for hospitalized patients with CAP is summarized in the following table (table 4). In addition to the tests recommended in the table, we recommend testing for
a specific organism when, based on clinical or epidemiologic data, pathogens that would not respond to usual empiric therapy are suspected (table 5) [2]. These include Legionella species,
seasonal influenza, avian (H5N1, H7N9) influenza, Middle East respiratory syndrome coronavirus, community-acquired methicillin-resistant S. aureus (CA-MRSA), Mycobacterium tuberculosis,
and agents of bioterrorism such as anthrax. [24]. (See "Diagnostic approach to community-acquired pneumonia in adults" and "Epidemiology, pathogenesis, and microbiology of community-
acquired pneumonia in adults".)
Tests that are indicated (especially sputum Gram stain and culture and blood cultures) should ideally be performed before antibiotics have been started. However, initiation of treatment should
not be delayed if it is not possible to obtain specimens immediately (eg, if the patient cannot produce a sputum specimen).
We also typically obtain a procalcitonin level at the time of diagnosis, and serially thereafter, to help guide antibiotic duration. (See 'Duration of therapy' below.)
INITIAL EMPIRIC THERAPY
Antibiotic therapy is typically begun on an empiric basis, since the causative organism is not identified in an appreciable proportion of patients (table 1 and table 2) [2,4,5,25]. The clinical
features and chest radiographic findings are not sufficiently specific to determine etiology and influence treatment decisions. (See "Epidemiology, pathogenesis, and microbiology of community-
acquired pneumonia in adults".)
The Gram stain of respiratory secretions can be useful for directing the choice of initial therapy if performed on a good quality sputum sample and interpreted by skilled examiners using
appropriate criteria [2]. (See "Diagnostic approach to community-acquired pneumonia in adults", section on 'Sputum'.)
Antibiotic recommendations for hospitalized patients with CAP are divided by the site of care (medical ward or intensive care unit [ICU]). Most hospitalized patients are initially treated with an
intravenous (IV) regimen. However, many patients without risk factors for severe pneumonia can be treated with oral therapy, especially with highly bioavailable agents such as the
fluoroquinolones [26]. (See 'Medical ward' below and 'Intensive care unit' below.)
The selection of antimicrobial regimens for empiric therapy is based upon a number of factors, including:
● The most likely pathogen(s) (see 'Likely pathogens' above)
● Clinical trials proving efficacy
● Risk factors for antimicrobial resistance (see 'Risk factors for Pseudomonas or drug-resistant pathogens' above)
● Medical comorbidities, which may influence the likelihood of a specific pathogen and may be a risk factor for treatment failure
● Epidemiologic factors such as travel and concurrent epidemics (eg, Middle East respiratory syndrome coronavirus, avian influenza) (see "Middle East respiratory syndrome coronavirus:
Virology, pathogenesis, and epidemiology" and "Epidemiology, transmission, and pathogenesis of avian influenza" and "Avian influenza A H7N9: Epidemiology, clinical manifestations, and
diagnosis")
Additional factors that may affect the choice of antimicrobial regimen include the potential for inducing antimicrobial resistance, pharmacokinetic and pharmacodynamic properties, safety
profile, and cost [13].
Antimicrobial initiation
Timing of antibiotics — We generally start antibiotic therapy as soon as we are confident that CAP is the appropriate working diagnosis and, ideally, within four hours of presentation for
patients being admitted to the general medical ward [2,27]. In patients with sepsis or septic shock, antibiotics should be started within one hour. (See "Evaluation and management of suspected
sepsis and septic shock in adults", section on 'Empiric antibiotic therapy (first hour)'.)
Although several studies have suggested a survival benefit to early initiation of antibiotics, some experts have questioned whether it is an independent risk factor for this outcome. It is important
to note, however, that a delay in antimicrobial therapy for seriously ill patients can adversely affect outcomes.
A 2016 systematic review included eight studies that evaluated time to initiation of antibiotics and noted that all of the studies were observational in design and therefore represented low-quality
evidence [28]. The four studies that showed an association between early initiation of antibiotics and reduced mortality were the largest of the studies, and three of them included patients ≥65
years of age with greater illness severity at presentation. In contrast, the four smallest studies included adults of all ages with less severe illness and found no association between early
antibiotic initiation and mortality.
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Two of the larger studies showed the following findings:
● In a retrospective study of 13,771 Medicare patients, antibiotic administration within four hours of hospital arrival was associated with reductions in mortality (6.8 compared with 7.4 percent
with delay in antibiotics) and length of stay (0.4 days shorter) [29].
● In a matched-propensity analysis of national data from the British Thoracic Society CAP audit that included 13,725 patients with CAP, adjusted 30-day inpatient mortality was lower for
adults who first received antibiotics in four or fewer hours compared with more than four hours (adjusted odds ratio 0.84, 95% CI 0.74-0.94) [30]. However, it is not clear whether early
antibiotics result in lower mortality or whether they are a marker for overall quality of care.
Route of administration — Generally, we favor administration of IV antibiotics for patients hospitalized for CAP at the start of therapy because of the high mortality associated with CAP and
the uncertainty of adequate gastrointestinal absorption or oral antibiotics in severely ill patients. Upon clinical improvement, IV antibiotics can be transitioned to oral therapy (see 'Switching to
oral therapy' below). Some experts use oral therapy when prescribing fluoroquinolones, macrolides, and doxycycline at the start of therapy in selected hospitalized patients without evidence or
risk of severe pneumonia because of the high oral bioavailability of these agents. The selection of specific antibiotic regimen varies based on severity of illness and risk factors for methicillin-
resistant S. aureus (MRSA) and Pseudomonas infection, as outlined below.
Medical ward
Without risk factors for resistance or Pseudomonas — For patients admitted to a general ward without risk factors for resistance, we suggest (table 6 and algorithm 2) [2,31]:
● Combination therapy with ceftriaxone (1 to 2 g IV daily), cefotaxime (1 to 2 g IV every 8 hours), ceftaroline (600 mg IV every 12 hours), ertapenem (1 g IV daily), or ampicillin-sulbactam
(1.5 to 3 g IV every 6 hours) plus a macrolide (azithromycin [500 mg IV or orally daily] or clarithromycin [500 mg twice daily] or clarithromycin XL [two 500 mg tablets once daily]).
Doxycycline (100 mg orally or IV twice daily) may be used as an alternative to a macrolide.
● Monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg IV or orally daily or moxifloxacin 400 mg IV or orally daily or gemifloxacin 320 mg orally daily) is an appropriate
alternative for patients who cannot receive a beta-lactam plus a macrolide.
Combination therapy with a beta-lactam plus a macrolide and monotherapy with a respiratory fluoroquinolone are of generally comparable efficacy for CAP overall [28,32-35]. However,
many observational studies have suggested that beta-lactam plus macrolide combination regimens are associated with better clinical outcomes in patients with severe CAP, possibly due to
the immunomodulatory effects of macrolides [36-39].
Furthermore, the severity of adverse effects (including the risk for Clostridioides [formerly Clostridium] difficile infection) and the risk of selection for resistance in colonizing organisms are
generally thought to be greater with fluoroquinolones than with the combination therapy regimens. For both of these reasons, we generally prefer combination therapy with a beta-lactam
plus a macrolide rather than monotherapy with a fluoroquinolone. Nevertheless, cephalosporins and other antibiotic classes also increase the risk of C. difficile infection. (See
"Clostridioides (formerly Clostridium) difficile infection in adults: Epidemiology, microbiology, and pathophysiology", section on 'Antibiotic use'.)
Recent antibiotic use should also inform the decision about the most appropriate regimen; if the patient has used a beta-lactam in the prior three months, a fluoroquinolone should be
chosen, if possible, and vice versa. (See 'Risk factors for Pseudomonas or drug-resistant pathogens' above.)
The approach to patients with penicillin allergy and/or cephalosporin allergy is presented below. (See 'Penicillin and cephalosporin allergy' below.)
With risk factors for resistance or Pseudomonas — If the patient has risk factors for Pseudomonas or drug-resistant pathogens, such as MRSA, coverage for these organisms should be
included, as discussed below. (See 'With risk factors for Pseudomonas or resistant gram-negative bacilli' below and 'With risk factors for MRSA' below.)
Penicillin and cephalosporin allergy — For penicillin-allergic patients, the type and severity of reaction should be assessed. Individuals with a past reaction to penicillin that was mild (not
Stevens Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms [DRESS]) and did not have features of an IgE-mediated reaction can receive
a broad-spectrum (third- or fourth-generation) cephalosporin or carbapenem safely.
Skin testing is indicated in some situations. Indications and strategies for skin testing are reviewed elsewhere. (See "Choice of antibiotics in penicillin-allergic hospitalized patients".)
For penicillin-allergic patients, if a skin test is positive or if there is significant concern to warrant avoidance of a cephalosporin or carbapenem, an alternative regimen should be given.
The appropriate regimen depends upon several factors, including the risk of Pseudomonas infection (algorithm 2):
● Patients without risk factors for Pseudomonas infection who are admitted to the general medical ward can be treated with a respiratory fluoroquinolone (levofloxacin 750 mg IV or orally
daily; moxifloxacin 400 mg IV or orally daily; gemifloxacin 320 mg orally daily).
Monotherapy with tigecycline is another alternative, but it should be limited to patients intolerant of both beta-lactams and fluoroquinolones since it has been associated with increased
mortality [40-42].
● Most patients with risk factors for Pseudomonas infection who are admitted to the general medical ward should receive levofloxacin (750 mg IV or orally daily) plus aztreonam (2 g IV
every 8 hours) plus an aminoglycoside (gentamicin, tobramycin, or amikacin). Patients with a prior life-threatening or anaphylactic reaction (involving urticaria, bronchospasm, and/or
hypotension) to ceftazidime should not be given aztreonam unless evaluated by an allergy specialist because of the possibility of cross-reactivity. Such patients can receive levofloxacin
plus an aminoglycoside for antipseudomonal coverage in the interim.
These regimens do not include an agent for community-acquired methicillin-resistant S. aureus (CA-MRSA). Agents for patients at risk for CA-MRSA are discussed below. (See 'With risk
factors for MRSA' below.)
Regimens for patients admitted to the ICU are presented below. (See 'Penicillin and cephalosporin allergy' below.)
Influenza therapy — Antiviral treatment is recommended as soon as possible for all persons with suspected or confirmed influenza requiring hospitalization or who have progressive,
severe, or complicated influenza infection, regardless of previous health or vaccination status [43]. (See "Treatment of seasonal influenza in adults".)
Intensive care unit — Patients requiring admission to an ICU are more likely to have risk factors for resistant pathogens, including CA-MRSA and Legionella spp [2,44]. Establishing an
etiologic diagnosis is particularly important in such patients. (See "Diagnostic approach to community-acquired pneumonia in adults".)
The approach to therapy is summarized in the following algorithm (algorithm 3) and discussed below.
Without risk factors for resistance or Pseudomonas — In patients without risk factors for or microbiologic evidence of P. aeruginosa or MRSA, we recommend IV combination therapy
with a potent anti-pneumococcal beta-lactam (ceftriaxone 1 to 2 g daily, cefotaxime 1 to 2 g every 8 hours, ceftaroline 600 mg every 12 hours, ampicillin-sulbactam 3 g every 6 hours, or
ertapenem 1 g IV daily) plus an advanced macrolide (azithromycin 500 mg daily) (table 6). Although the optimal doses of the beta-lactams (ceftriaxone, cefotaxime, ampicillin-sulbactam) have
not been studied adequately, we favor the higher doses, at least initially, until the minimum inhibitory concentrations (MICs) against possible isolates (eg, S. pneumoniae) are known.
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For the second agent, an alternative to azithromycin is a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). Regimens containing either a macrolide or
fluoroquinolone have been generally comparable in clinical trials [31,45-47]. However, many observational studies have suggested that macrolide-containing regimens are associated with
better clinical outcomes for patients with severe CAP, possibly due to immunomodulatory effects of macrolides [36-39]. For this reason, we generally favor a macrolide-containing regimen
in this setting, unless there is a specific reason to avoid macrolides, such as patient allergy or intolerance.
Furthermore, the severity of adverse effects (including the risk for C. difficile infection) and the risk of selection for resistance in colonizing organisms are generally thought to be greater with
fluoroquinolones than with other antibiotic classes. Nevertheless, cephalosporins and other antibiotic classes also increase the risk of C. difficile infection. (See "Clostridioides (formerly
Clostridium) difficile infection in adults: Epidemiology, microbiology, and pathophysiology", section on 'Antibiotic use'.)
Recent antibiotic use should also inform the decision about the most appropriate regimen. (See 'Risk factors for Pseudomonas or drug-resistant pathogens' above.)
With risk factors for Pseudomonas or resistant gram-negative bacilli — In patients who may be infected with P. aeruginosa or other resistant gram-negative pathogens (particularly
those with structural lung abnormalities [eg, bronchiectasis], chronic obstructive pulmonary disease [COPD] and frequent antimicrobial or glucocorticoid use, and/or gram-negative bacilli seen
on sputum Gram stain), empiric therapy should include agents effective against pneumococcus, P. aeruginosa, and Legionella spp. However, if P. aeruginosa or another resistant gram-negative
pathogen is not isolated, coverage for these organisms should be discontinued. Acceptable regimens include combination therapy with an antipseudomonal/anti-pneumococcal beta-lactam
antibiotic and an antipseudomonal fluoroquinolone, such as the following regimens:
● Piperacillin-tazobactam (4.5 g every six hours) or
● Imipenem (500 mg IV every six hours) or
● Meropenem (1 g every eight hours) or
● Cefepime (2 g every eight hours) or
● Ceftazidime (2 g every eight hours; activity against pneumococcus more limited than agents listed above)
PLUS
● Ciprofloxacin (400 mg every eight hours) or
● Levofloxacin (750 mg daily)
The dose of levofloxacin is the same when given intravenously and orally, while the dose of ciprofloxacin is 750 mg orally twice daily. (See "Fluoroquinolones", section on 'Pharmacokinetics'.)
With risk factors for MRSA — Empiric therapy for community-acquired methicillin-resistant S. aureus (CA-MRSA) should be given to hospitalized patients with septic shock or respiratory
failure requiring mechanical ventilation. We also suggest empiric therapy of MRSA in patients with CAP who have any of the following risk factors: gram-positive cocci in clusters seen on
sputum Gram stain, known colonization with MRSA, risk factors for colonization with MRSA (eg, end-stage renal disease, contact sport participants, injection drug users, those living in crowded
conditions, men who have sex with men, prisoners), recent influenza-like illness, antimicrobial therapy (particularly with a fluoroquinolone) in the prior three months, necrotizing or cavitary
pneumonia, or presence of empyema.
In such patients, we recommend treatment for MRSA with the addition of vancomycin (15 mg/kg IV every 12 hours, adjusted to a trough level of 15 to 20 mcg/mL and for renal function; in
seriously ill patients, a loading dose of 25 to 30 mg/kg may be given) or linezolid (600 mg IV every 12 hours) until the results of culture and susceptibility testing are known. Clindamycin (600
mg IV or orally three times daily) may be used as an alternative to vancomycin or linezolid if the isolate is known to be susceptible. Ceftaroline is active against most strains of MRSA but is not
US Food and Drug Administration (FDA) approved for pneumonia caused by S. aureus. If MRSA is not isolated, coverage for this organism should be discontinued. (See 'Community-acquired
MRSA' below.)
The combination of vancomycin and piperacillin-tazobactam has been associated with acute kidney injury. In patients who require an anti-MRSA agent and an
antipseudomonal/anti-pneumococcal beta-lactam, options include using a beta-lactam other than piperacillin-tazobactam (eg, cefepime or ceftazidime) or, if piperacillin-tazobactam is favored,
using linezolid instead of vancomycin. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults", section on 'Nephrotoxicity'.)
Penicillin and cephalosporin allergy — As noted above, for penicillin-allergic patients, the type and severity of reaction should be assessed. (See 'Penicillin and cephalosporin allergy'
above.)
For penicillin-allergic patients, if a skin test is positive or if there is significant concern to warrant avoidance of a cephalosporin or carbapenem, an alternative regimen should be given.
The appropriate regimen depends upon several factors, including the risk of Pseudomonas infection (algorithm 3):
● For most patients without risk factors for Pseudomonas infection who are admitted to the ICU, a respiratory fluoroquinolone plus aztreonam (2 g IV every 8 hours) should replace the
beta-lactams recommended for those without penicillin allergy.
Ceftazidime and aztreonam have similar side chain groups, and cross-reactivity between the two drugs is variable. Patients with a prior life-threatening or anaphylactic reaction (involving
urticaria, bronchospasm, and/or hypotension) to ceftazidime should not be given aztreonam unless evaluated by an allergy specialist because of the possibility of cross-reactivity. Such
patients can receive levofloxacin plus an aminoglycoside for antipseudomonal coverage in the interim.
The prevalence of cross-sensitivity between ceftazidime and aztreonam has been estimated at <5 percent of patients, based upon limited data. A reasonable approach in those with mild
past reactions to ceftazidime (eg, uncomplicated maculopapular rash) would involve informing the patient of the low risk of cross-reactivity and administering aztreonam with a graded
challenge (1/10 dose followed by a one-hour period of observation; if no symptoms, give the full dose followed by another hour of observation). (See "Cephalosporin-allergic patients:
Subsequent use of cephalosporins and related antibiotics" and "An approach to the patient with drug allergy", section on 'Graded challenge'.)
● Most patients with risk factors for Pseudomonas infection who are admitted to the ICU should receive levofloxacin (750 mg IV or orally daily) plus aztreonam (2 g IV every 8 hours) plus an
aminoglycoside (gentamicin, tobramycin, or amikacin). Patients with a prior life-threatening or anaphylactic reaction (involving urticaria, bronchospasm, and/or hypotension) to ceftazidime
should not be given aztreonam unless evaluated by an allergy specialist because of the possibility of cross-reactivity. Such patients can receive levofloxacin plus an aminoglycoside for
antipseudomonal coverage in the interim.
These regimens do not include an agent for CA-MRSA. Agents for patients at risk for CA-MRSA are discussed below. (See 'Community-acquired MRSA' below.)
Adjunctive glucocorticoids — The use of glucocorticoids as an adjunctive treatment for CAP is controversial. The rationale for treating patients with CAP is to reduce the inflammatory
response to pneumonia, which may contribute to its morbidity and mortality. However, the population that may benefit most from this intervention is not well defined, and adverse effects are
potentially severe.
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● For patients with CAP who have evidence of an exaggerated or dysregulated host inflammatory response, defined as sepsis or respiratory failure with an FiO2 requirement of >50 percent
plus one or more of the following features (metabolic acidosis with an arterial pH of <7.3, lactate >4 mmol/L, or a C-reactive protein >150 mg/L), we suggest giving adjunctive
glucocorticoids. These patients are at high risk of mortality and are likely to benefit the most.
Reasons to avoid glucocorticoids in such patients include risk factors for severe adverse events such as recent gastrointestinal bleeding, poorly controlled diabetes, or severe
immunocompromise. We also avoid glucocorticoids in patients with CAP known to be caused by a viral pathogen such as influenza or a fungal pathogen such as Aspergillus.
● For other hospitalized patients, we make the decision on a case-by-case basis but generally find that the potential for harm outweighs the potential for benefit in patients who are at low risk
for mortality.
When using adjunctive glucocorticoids, we generally use methylprednisolone 0.5 mg/kg IV every 12 hours and treat for a total of five days.
These recommendations are based on the results of several meta-analyses that demonstrate a possible mortality benefit with glucocorticoid use in hospitalized patients with CAP [48-54]. This
mortality benefit appears to be highest in patients with severe CAP, with an absolute risk reduction of 5 percent reported in one meta-analysis (risk ratio [RR] 0.39, 95% CI 0.20-0.77) [48]. In
another meta-analysis, based on individual patient data, the absolute risk reduction was smaller (3.2 percent) and did not reach statistical significance (RR 0.70, 95% CI 0.44-1.13). In each
meta-analysis, risk reductions were estimated from subgroup analyses of small randomized trials evaluating <600 patients in total. Concerns have been raised about the methodologic
limitations of included trials [55-58] and the appropriateness of compiling these studies [59,60]. Our confidence in the estimated risk reductions is therefore moderate to low.
Meta-analyses have demonstrated a possible mortality benefit among all hospitalized patients with CAP. However, the benefit appears modest and has been inconsistently demonstrated
[48-54]. One meta-analysis evaluating 12 randomized trials involving over 1900 patients hospitalized with CAP showed a 2.6 percent absolute reduction in mortality in patients who received
glucocorticoids compared with placebo (5.3 versus 7.9 percent; RR 0.67, 95% CI 0.45-1.01) [48]. However, the detected risk reduction was largely driven by the mortality benefit observed in
patients with severe CAP, and it is unclear if this finding is broadly generalizable.
Harms associated with glucocorticoid use in this setting have not been well studied. While an increase in serious adverse events with glucocorticoid use was not detected in the above meta-
analyses [48-52], most trials excluded patients at risk for adverse events, including immunocompromised patients, pregnant women, patients who had recent gastrointestinal bleeding, and
patients at increased risk of neuropsychiatric side effects [48]. Hyperglycemia was consistently reported with corticosteroid use when compared with placebo [48,53]. Observational data also
suggest that short-term glucocorticoid use may lead to additional harm such as fracture or thromboembolism with widespread use [61].
Whether the benefits and harms of glucocorticoids vary with the causative pathogen is uncertain. In patients with influenza infection and Aspergillus infection, glucocorticoid use has been
associated with worse outcomes [62,63]. We therefore avoid glucocorticoid use in patients with CAP caused by another viral or fungal pathogen. Because glucocorticoids have an
immunosuppressive effect, we also avoid glucocorticoid use in patients with CAP that is caused by a pathogen for which no antimicrobial therapy is available (eg, most viral pneumonias).
In order to resolve some of the uncertainty in this area, a large clinical trial evaluating whether or not glucocorticoids improve outcomes in critically ill patients is underway [64].
Influenza therapy — Antiviral treatment is recommended as soon as possible for all persons with suspected or confirmed influenza requiring hospitalization or who have progressive,
severe, or complicated influenza infection, regardless of previous health or vaccination status [43]. (See "Treatment of seasonal influenza in adults".)
SUBSEQUENT MANAGEMENT
Clinical response to therapy — With appropriate antibiotic therapy, some improvement in the patient's clinical course is usually seen within 48 to 72 hours (table 7). Patients who do not
demonstrate some clinical improvement within 72 hours are considered nonresponders.
The time course of the clinical response to therapy is illustrated by the following observations:
● In a prospective, multicenter cohort study of 686 adults hospitalized with CAP, the median time to becoming afebrile was two days when fever was defined as 38.3ºC (101ºF) and three
days when defined as either 37.8ºC (100ºF) or 37.2ºC (99ºF) [65]. However, fever in patients with lobar pneumonia may take three days or longer to improve.
● In a second prospective multicenter trial of 1424 patients hospitalized with CAP, the median time to stability (defined as resolution of fever, heart rate <100 beats/minute, respiratory rate
<24 breaths/minute, systolic blood pressure of ≥90 mmHg, and oxygen saturation ≥90 percent for patients not receiving prior home oxygen) was four days [66].
Although a clinical response to appropriate antibiotic therapy is seen relatively quickly, the time to resolution of all symptoms and radiographic findings is more prolonged. With pneumococcal
pneumonia, for example, the cough usually resolves within eight days, and auscultatory crackles clear within three weeks. (See "Pneumococcal pneumonia in adults".)
In addition, as many as 87 percent of inpatients with CAP have persistence of at least one pneumonia-related symptom (eg, fatigue, cough with or without sputum production, dyspnea, chest
pain) at 30 days compared with 65 percent by history in the month prior to the onset of CAP [67]. Patients should be told that some symptoms can last this long so that they are able to set
reasonable expectations for their clinical course. (See "Prognosis of community-acquired pneumonia in adults", section on 'Mortality and symptom resolution'.)
Issues relating to nonresolving pneumonia are discussed in detail separately. (See "Nonresolving pneumonia".)
Radiographic response — Radiographic improvement typically lags behind the clinical response [16,68-70]. This issue was addressed in a prospective multicenter trial of 288 patients
hospitalized for severe CAP; the patients were followed for 28 days in order to assess the timing of resolution of chest radiograph abnormalities [68]. The following findings were noted:
● At day 7, 56 percent had clinical improvement but only 25 had resolution of chest radiograph abnormalities.
● At day 28, 78 percent had attained clinical cure but only 53 percent had resolution of chest radiograph abnormalities. The clinical outcomes were not significantly different between patients
with and without deterioration of chest radiograph findings during the follow-up period.
● Delayed radiographic resolution was independently associated with multilobar disease.
In other studies, the timing of radiologic resolution of the pneumonia varied with patient age and the presence of underlying lung disease [69,70]. The chest radiograph usually cleared within
four weeks in patients younger than 50 years of age without underlying pulmonary disease. In contrast, resolution could be delayed for 12 weeks or more in older individuals and in those with
underlying lung disease.
Patients who respond to therapy
Narrowing therapy — If a pathogen has been established based upon reliable microbiologic methods and there is no laboratory or epidemiologic evidence of coinfection, we recommend
narrowing therapy ("de-escalation") to target the specific pathogen in order to avoid antibiotic overuse. The results of diagnostic studies that provide identification of a specific etiology within 24
to 72 hours can be useful for guiding continued therapy. (See "Diagnostic approach to community-acquired pneumonia in adults".)
Pathogen-specific therapy for specific organisms is summarized in the table and discussed in greater detail separately (table 8). (See "Pneumococcal pneumonia in adults" and "Mycoplasma
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pneumoniae infection in adults" and "Pneumonia caused by Chlamydia pneumoniae in adults" and "Treatment and prevention of Legionella infection" and "Pseudomonas aeruginosa
pneumonia" and "Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection" and "Treatment of seasonal influenza in adults".)
In a randomized trial, pathogen-directed treatment (PDT) was compared with empiric broad-spectrum antibiotic treatment (EAT) in 262 hospitalized patients with CAP [71]. PDT was based
upon microbiologic studies (rapid diagnostic tests) or clinical presentation; EAT patients received a beta-lactam-beta-lactamase inhibitor plus erythromycin or, if admitted to the intensive care
unit (ICU), ceftazidime and erythromycin. Overall, clinical outcomes (length of stay, 30-day mortality, fever resolution, and clinical failure) were the same for both groups. Adverse events were
more frequent in the EAT group but were primarily related to the specific antimicrobial choice (ie, erythromycin).
Switching to oral therapy — Patients requiring hospitalization for CAP are generally begun on intravenous (IV) therapy (see 'Route of administration' above). They can be switched to oral
therapy when they are improving clinically, hemodynamically stable, able to take oral medications, and have a normally functioning gastrointestinal tract (algorithm 4) [2].
If the pathogen has been identified, the choice of oral antibiotic therapy is based upon the susceptibility profile (table 8). If a pathogen is not identified, the choice of antibiotic for oral therapy is
usually either the same as the IV antibiotic or in the same drug class. If S. aureus, Pseudomonas, or a resistant gram-negative bacillus have not been isolated from a good quality sputum
specimen, then empiric therapy for these organisms is not necessary. (See "Sputum cultures for the evaluation of bacterial pneumonia".)
The choice of oral regimen depends on the risk of drug-resistant S. pneumoniae and on the initial IV regimen:
● In patients who are treated with the combination of an IV beta-lactam and a macrolide who have risk factors for drug-resistant S. pneumoniae (DRSP), we replace the IV beta-lactam with
high-dose amoxicillin (1 g orally three times daily) to complete the course of therapy. When DRSP is not a concern, amoxicillin can be given at a dose of 500 mg orally three times daily or
875 mg orally twice daily. In patients who have already received 1.5 g of azithromycin who do not have Legionella pneumonia, we do not continue atypical coverage. Conversely, in
patients who have not received 1.5 g of azithromycin, we give amoxicillin in combination with a macrolide or doxycycline. An alternative for patients without risk factors for DRSP is to give
a macrolide or doxycycline alone to complete the course of therapy. The dosing for macrolides and doxycycline is as follows (see 'Risk factors for Pseudomonas or drug-resistant
pathogens' above and "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Treatment regimens'):
• Azithromycin – 500 mg once daily
• Clarithromycin – 500 mg twice daily
• Clarithromycin XL – Two 500 mg tablets (1000 mg) once daily
• Doxycycline – 100 mg twice daily
● Patients who are treated initially with an IV respiratory fluoroquinolone can switch to the oral formulation of the same agent (eg, levofloxacin 750 mg once daily or moxifloxacin 400 mg
once daily) to complete the course of therapy.
The duration of therapy is discussed below. (See 'Duration of therapy' below.)
Two prospective observational studies in 253 patients evaluated the clinical outcome of an early switch from IV to oral therapy in the treatment of CAP [72,73]. Patients met the following criteria
prior to switching: resolution of fever, improvement in respiratory function, decrease in white blood cell count, and normal gastrointestinal tract absorption. Only two patients failed treatment,
and the protocol was associated with high patient satisfaction [73].
Similar outcomes were noted in a multicenter randomized trial in the Netherlands of 265 patients with CAP (mean age 70) admitted to non-intensive care wards [74]. Patients were initially
treated with three days of IV antibiotics and, when clinically stable, were assigned either to oral antibiotics to complete a total course of 10 days or to a standard regimen of 7 days of IV
antibiotics. There was no difference in 28-day mortality (4 versus 2 percent) or clinical cure rate (83 versus 85 percent), while the length of hospital stay was reduced in the oral switch group by
a mean of 1.9 days (9.6 versus 11.5 days).
In another randomized trial, a three-step pathway that involved early mobilization of patients in combination with the use of objective criteria for switching to an oral antibiotic regimen and for
deciding on hospital discharge was compared to usual care [75]. The median length of stay was significantly shorter in the patients who were assigned to the three-step pathway (3.9 versus 6.0
days). In addition, the median duration of IV antibiotics was significantly shorter in the patients who were assigned to the three-step pathway (2.0 versus 4.0 days). More patients assigned to
usual care experienced adverse drug reactions (4.5 versus 16 percent). No significant differences were observed in the rate of readmission, the case-fatality rate, or patients' satisfaction with
care.
Documentation of pneumococcal bacteremia does not appear to alter the effect of switching to oral therapy early (no clinical failures in 18 such patients switched based upon the above criteria
in one report) [76].
Duration of hospitalization — Hospital discharge is appropriate when the patient is clinically stable from the pneumonia, can take oral medication, has no other active medical problems,
and has a safe environment for continued care; patients do not need to be kept overnight for observation following the switch. Early discharge based on clinical stability and criteria for switch to
oral therapy is encouraged to reduce unnecessary hospital costs and hospital-associated risks, including iatrogenic complications and greater risk for antimicrobial resistance.
Several studies have shown that it is not necessary to observe stable patients overnight after switching from IV to oral therapy, although this has been common practice [2,77,78]. As an
example, a retrospective review of the United States Medicare National Pneumonia Project database compared outcomes between patients hospitalized for CAP who were not (n = 2536) and
who were (n = 2712) observed overnight after switching to oral therapy [78]. The following findings were noted:
● No significant difference in 14-day hospital readmission rate (7.8 versus 7.2 percent)
● No significant difference in the 30-day mortality rate (5.1 versus 4.4 percent)
The importance of clinical stability at discharge was illustrated in a prospective observational study of 373 Israeli patients discharged with a diagnosis of CAP [79]. On the last day of
hospitalization, seven parameters of instability were evaluated (temperature >37.8ºC [100ºF], respiratory rate [RR] >24 breaths/minute, heart rate [HR] >100 beats/minute, systolic blood
pressure [SBP] ≤90 mmHg, oxygen saturation <90 percent on room air, inability to receive oral nutrition, and change of mental status from baseline). At 60 days post discharge, patients with at
least one parameter of instability at discharge were significantly more likely to have died or required readmission than patients with no parameters of instability (death rates 14.6 versus 2.1
percent; readmission rates 14.6 versus 6.5 percent).
As noted above, in one trial, a three-step pathway that involved early mobilization of patients in combination with the use of objective criteria for switching to an oral antibiotic regimen and for
deciding on hospital discharge was compared with usual care [75]. The median length of stay was significantly shorter in the patients who were assigned to the three-step pathway (3.9 versus
6.0 days).
Duration of therapy — Based upon the available data, we agree with the recommendation of the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS)
guidelines that patients with CAP should be treated for a minimum of five days [2,5]. Before stopping therapy, the patient should be afebrile for 48 to 72 hours, breathing without supplemental
oxygen (unless required for pre-existing disease), and have no more than one clinical instability factor (defined as HR >100 beats/minute, RR >24 breaths/minute, and SBP ≤90 mmHg)
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(algorithm 5) [2]. Most patients become clinically stable within three to four days of starting antibiotic treatment [65,66,80]. Thus, the recommended duration for patients with good clinical
response within the first two to three days of therapy is usually five to seven days total.
In addition, we use procalcitonin to help guide the decision to stop antibiotics (algorithm 6). We generally obtain a level at the time of diagnosis and repeat the level every two days in patients
who are clinically stable. We determine the need for continued antibiotic therapy based on clinical improvement, serial procalcitonin levels, microbiologic diagnosis, and the presence of
complications. (See "Procalcitonin use in lower respiratory tract infections", section on 'Community-acquired pneumonia'.)
Longer duration of therapy is needed for certain patients even if they are clinically stable and procalcitonin levels are low:
● If the initial therapy was not active against the subsequently identified pathogen (see 'Clinical response to therapy' above)
● If extrapulmonary infection is identified (eg, meningitis or endocarditis)
● If the patient has pneumonia caused by P. aeruginosa or pneumonia caused by some unusual and less common pathogens (eg, Burkholderia pseudomallei, fungus) (see "Pseudomonas
aeruginosa pneumonia", section on 'Directed antimicrobial therapy' and "Treatment and prevention of Legionella infection" and "Treatment and prevention of Legionella infection", section
on 'Treatment of other Legionella infections')
● If the patient has necrotizing pneumonia, empyema, or lung abscess [81]
Longer treatment durations (eg ≥7 days) should also be considered for patients with parapneumonic effusions. Patients with uncomplicated effusions can typically be treated with antibiotics
alone. For these patients, we typically treat until there is both clear clinical and radiographic response, which often requires a 7- to 14-day course of therapy. The intent of the longer course is to
prevent relapse and/or the development of empyema. For those with complicated parapneumonic effusions, drainage in addition to a longer course of antibiotics is needed for cure.
The duration of therapy in these patients should be individualized based upon the clinical response to treatment and patient comorbidities. For the treatment of methicillin-resistant S. aureus
(MRSA) pneumonia without metastatic infection, duration will vary. For patients with MRSA pneumonia without complications (eg, bacteremia), we generally treat for approximately seven days,
provided that they are responding to therapy within 72 hours of starting treatment. For patients with MRSA pneumonia complicated by bacteremia, a minimum of two weeks of treatment is
needed. Longer courses (eg, ≥4 weeks) are needed for patients with metastatic complications of bacteremia. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of
bacteremia".)
Several meta-analyses support a 5- to 7-day antibiotic treatment regimen for most patients with CAP. In one meta-analysis of 21 trials evaluating 4861 patients with CAP, no significant
difference in clinical cure or relapse rates were detected when comparing antibiotic durations of ≤6 days versus durations of ≥7 days [82-84]. Subgroup analyses suggest that these findings
hold true regardless of treatment setting or disease severity. However, the number of patients with severe pneumonia included in the meta-analysis was likely small. Mortality and serious
adverse event rates were lower among those treated with shorter courses (risk ratio [RR] 0.52, 95% CI 0.33-0.82 and RR 0.73, 95% CI 0.55-0.97, respectively). Trials included in this analysis
compared antibiotics from different classes and/or antibiotics with different half-lives, which may confound results. However, in a previous meta-analysis of five randomized trials evaluating
adults with CAP comparing short (3 to 7 days) versus long (7 to 10 days) antibiotic courses, no differences in clinical success, relapse, or mortality were detected [83].
In a multicenter trial designed to validate the IDSA/ATS guidelines on antibiotic duration for CAP, 312 hospitalized patients with CAP were randomized to an intervention or control group on day
5 of antibiotic therapy [85]. In the intervention group, antibiotics were discontinued for patients whose temperature was ≤37.8°C (100°F) for at least 48 hours and who had no more than one
CAP-associated sign of clinical instability. In the control group, antibiotic duration was determined by the treating physician. Antibiotic duration was shorter in the intervention group (median 5
versus 10 days); 70 percent of patients in the intervention group received only five days of antibiotics compared with 3 percent in the control group. In the intention-to-treat analysis, clinical
success was similar in the intervention group and the control group at day 10 (56 versus 49 percent) and day 30 (92 versus 89 percent). Mean CAP symptom questionnaire scores were similar
between the intervention and control groups at days 5 and 10. There were also no differences in the secondary outcomes of in-hospital mortality, 30-day mortality, and pneumonia recurrence.
Readmission at day 30 was less common in the intervention group than in the control group (1 versus 7 percent).
Patients are often treated with antibiotics for longer than necessary [86]. Antimicrobial stewardship programs can help to shorten the duration of antibiotics and narrow the spectrum of
antibiotics [87]. (See "Antimicrobial stewardship in hospital settings".)
Clinical follow-up after discharge — Patients who have been discharged from the hospital with CAP should have a follow-up visit, usually within one week. In addition, a later visit is often
indicated to assess for resolution of pneumonia.
Follow-up chest radiograph — Most patients with clinical resolution after treatment do not require a follow-up chest radiograph. We perform chest radiograph at 7 to 12 weeks following
treatment in patients >50 years of age, particularly in males and smokers in this age group [88].
Chest radiograph is performed in this relatively higher risk population in order document resolution of the pneumonia and to exclude underlying diseases, particularly malignancy. In a large
population-based cohort study of patients with CAP, new lung cancer was diagnosed within 90 days of CAP in 1.1 percent and within 5 years in 2.3 percent [89]. On multivariate analysis, the
characteristic most strongly associated with lung cancer was age >50 years (adjusted hazard ratio [aHR] 19.0, 95% CI 5.7-63.6); other risk factors were male sex (aHR 1.8, 95% CI 1.1-2.9)
and smoking (aHR 1.7, 95% CI 1.0-3.0).
SPECIFIC CONSIDERATIONS
Community-acquired MRSA — As discussed above, empiric therapy for community-acquired methicillin-resistant S. aureus (CA-MRSA) should be given to hospitalized patients with septic
shock or respiratory failure requiring mechanical ventilation. It should also be given to those with risk factors for MRSA. (See 'Methicillin-resistant Staphylococcus aureus' above.)
We generally prefer linezolid over vancomycin when CA-MRSA is suspected (eg, young, otherwise healthy patient who plays contact sports presenting with necrotizing pneumonia) because of
linezolid's ability to inhibit bacterial toxin production [90]. However, in each case, we select between these agents based on other factors such as renal function, monitoring convenience,
potential drug interactions (eg, linezolid can interact with selective serotonin-reuptake inhibitors), blood cell counts, and quality of intravenous access.
The data regarding the therapy of pneumonia caused by CA-MRSA are limited. A randomized trial showed superiority in clinical outcomes, but not mortality, of linezolid compared with
vancomycin in hospital-acquired or health care-associated pneumonia caused by MRSA [90]. In contrast, in a meta-analysis of nine randomized trials of patients with hospital-acquired
pneumonia that compared linezolid and vancomycin, there were no differences in mortality or clinical response [91]. The treatment of MRSA pneumonia is discussed in detail separately. (See
"Treatment of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Methicillin-resistant Staphylococcus aureus'.)
Although CA-MRSA is typically susceptible to more antibiotics than hospital-acquired MRSA, it appears to be more virulent [92]. CA-MRSA often causes a necrotizing pneumonia [93,94]. The
strain causing CA-MRSA is known as "USA 300" and the gene for Panton-Valentine leukocidin (PVL) characterizes this strain [95-99]. However, an animal study suggests that the virulence of
CA-MRSA strains is probably not due to PVL [100]. In addition, one study of patients with hospital-acquired pneumonia due to MRSA observed that the severity of infection and clinical outcome
was not influenced by the presence of the PVL gene [101]. It is possible that other cytolytic toxins play a role in the pathogenesis of CA-MRSA infections. Vancomycin does not decrease toxin
production, whereas linezolid has been shown to reduce toxin production in experimental models [102,103]. (See "Virulence determinants of community-acquired methicillin-resistant
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Staphylococcus aureus".)
One concern with vancomycin is the increasing minimum inhibitory concentrations (MICs) of MRSA that have emerged in recent years, which may reduce the efficacy of vancomycin in
pulmonary infection. In patients with a MRSA isolate with an increased vancomycin MIC (>2 mcg/mL), we prefer linezolid. Vancomycin-intermediate and vancomycin-resistant S. aureus
infection is discussed in greater detail separately. (See "Staphylococcus aureus bacteremia with reduced susceptibility to vancomycin".)
When vancomycin is used, trough concentrations should be monitored in order to ensure that a target trough concentration between 15 and 20 mcg/mL is achieved. There may be important
differences in potency and toxicity based on the supply source of generic formulations of vancomycin [104]. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)
Factors associated with rapid mortality include infection with influenza, the need for ventilator or inotropic support, onset of respiratory distress syndrome, hemoptysis, and leukopenia. In a
report of 51 cases of CAP caused by S. aureus (79 percent of which were MRSA), 39 percent had a white blood cell [WBC] count <4000/microL, and this finding was associated with a poor
prognosis. In contrast, a WBC >10,000/microL appeared to be protective [105].
If a sputum culture reveals methicillin-susceptible S. aureus (MSSA), therapy should be changed to nafcillin (2 g IV every four hours) or oxacillin (2 g IV every four hours) (table 8).
Atypical bacteria — The value of providing empiric coverage for atypical pathogens (eg, M. pneumoniae, C. pneumoniae, Legionella spp) is debated [32,106]. One reason for this is that
testing for M. pneumoniae and C. pneumoniae is not usually done and, until 2012, there were no US Food and Drug Administration (FDA)-cleared polymerase chain reaction tests to detect
them. Thus, their role in an individual case or in population-based studies is not well elucidated. (See "Treatment and prevention of Legionella infection", section on 'Empiric treatment' and
"Diagnostic approach to community-acquired pneumonia in adults", section on 'Chlamydia pneumoniae' and "Diagnostic approach to community-acquired pneumonia in adults", section on
'Mycoplasma pneumoniae'.)
Adverse effects — Both the macrolides and the fluoroquinolones can cause a prolonged QT interval, which can result in torsades de pointes and death. Studies assessing the risk-benefit ratio
of azithromycin are reviewed elsewhere. Since the use of macrolides (and azithromycin in particular) has been associated with reduced mortality in CAP patients who require hospitalization,
the risks and benefits should be considered when selecting a regimen. For the general population, azithromycin can be prescribed without significant concern; for patients at high risk of QT
interval prolongation, the use of azithromycin should be weighed against the risk of cardiac effects. For patients with known QT interval prolongation, we favor doxycycline since it has not been
associated with QT interval prolongation. However, doxycycline should be avoided during pregnancy. It should also be noted that doxycycline has been less well studied for the treatment of
CAP than the macrolides and fluoroquinolones. Patients at particular risk for QT prolongation include those with existing QT interval prolongation, hypokalemia, hypomagnesemia, significant
bradycardia, bradyarrhythmias, uncompensated heart failure, and those receiving certain antiarrhythmic drugs (eg, class IA [quinidine, procainamide] or class III [dofetilide, amiodarone, sotalol]
antiarrhythmic drugs). Older adult patients may also be more susceptible to drug-associated QT interval prolongation. (See "Fluoroquinolones", section on 'QT interval prolongation and
arrhythmia' and "Acquired long QT syndrome: Definitions, causes, and pathophysiology" and "Pharmacology of azoles", section on 'Selected clinical effects' and "Azithromycin, clarithromycin,
and telithromycin", section on 'QT interval prolongation and cardiovascular events'.)
There is concern that widespread use of fluoroquinolones will promote the development of fluoroquinolone resistance among respiratory pathogens (as well as other colonizing pathogens) and,
as noted above, increases the risk of C. difficile colitis. In addition, empiric use of fluoroquinolones should not be used for patients at risk for M. tuberculosis without an appropriate assessment
for tuberculosis infection. The administration of a fluoroquinolone in patients with tuberculosis has been associated with a delay in diagnosis, increase in resistance, and poor outcomes
[107-111]. (See "Clostridioides (formerly Clostridium) difficile infection in adults: Epidemiology, microbiology, and pathophysiology", section on 'Antibiotic use'.)
Risk factors for rehospitalization — Risk factors for rehospitalization were assessed in a multicenter randomized trial of hospitalized patients with CAP [112]. Among 577 patients, 70 (12
percent) were rehospitalized within 30 days, 52 were related to comorbidities (most commonly cardiovascular, pulmonary, or neurologic), and 14 were related to pneumonia. Factors that were
independently associated with rehospitalization included less than a high school education, unemployment, coronary artery disease, and chronic obstructive pulmonary disease.
In a similar study of 1117 patients from a single center, 81 (7 percent) were rehospitalized within 30 days; 29 due to pneumonia-related causes and the remainder due to pneumonia-unrelated
causes [113]. Risk factors for pneumonia-related rehospitalization were initial treatment failure and one or more instability factors (eg, vital signs or oxygenation) on discharge; risk factors for
non-pneumonia-related readmissions were age ≥65 and decompensated comorbidities (most commonly cardiac or pulmonary).
NEW ANTIMICROBIAL AGENTS
Several new agents are available or in the development for the treatment of CAP. These include omadacycline (a tetracycline derivative), delafloxacin (an extended-spectrum fluoroquinolone),
and lefamulin (a systemic pleuromutilin). Because these agents are not yet well studied, particularly in patients with severe CAP, we generally reserve their use for situations in which alternate
treatment options are not available or pose risk of adverse effects (eg, drug allergy or intolerance).
Omadacycline is US Food and Drug Administration (FDA) approved for the treatment of CAP and has activity against common atypical and typical CAP pathogens, methicillin-resistant S.
aureus (MRSA), many gram-negative rods (but not Pseudomonas spp), and anaerobes [114]. Because of its broad spectrum, it is a potential alternative treatment option for mild or moderate
aspiration pneumonia if pseudomonal infection is not suspected.
Delafloxacin has activity against many respiratory pathogens including MRSA and Pseudomonas spp but is not yet FDA approved for the treatment of respiratory tract infections [115].
Lefamulin has a narrower spectrum, which includes MRSA, S. pneumoniae, and atypical CAP pathogens. However, apart from H. influenza and Moraxella catarrhalis, its activity against gram-
negative pathogens including Pseudomonas spp is limited [116].
PREVENTIVE MEASURES
Vaccination — Patients with CAP should be appropriately vaccinated for influenza and pneumococcal infection [2]. Screening for influenza vaccination status is warranted during influenza
season (eg, from October through March in the northern hemisphere) in all patients. Screening for pneumococcal vaccination status is warranted in patients age 65 or older or with other
indications for vaccination (table 9). Vaccination can be administered at any time during hospitalization after the patient has become stable. (See "Seasonal influenza vaccination in adults" and
"Pneumococcal vaccination in adults".)
Smoking cessation — Smoking cessation should be a goal for hospitalized patients with CAP who smoke [2]. (See "Overview of smoking cessation management in adults".)
Fall prevention — It is important to ensure that patients, particularly older patients, are mobilized early and often during their hospitalization to prevent falls and reduce functional decline. (See
"Hospital management of older adults", section on 'Early mobilization programs'.)
GUIDELINES
A number of medical societies have issued guidelines for the treatment of CAP [2,117-119]. The antibiotic regimens advocated by a collaboration between the Infectious Diseases Society of
America (IDSA)/American Thoracic Society (ATS) in 2007 [2] and the British Thoracic Society (BTS) in 2009 [117] are summarized in the tables (table 6 and table 10).
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The recommendations in this topic are generally in keeping with the IDSA/ATS guidelines. Recommendations from these and other guidelines are summarized as follows:
● For hospitalized patients on the general wards, the IDSA/ATS guidelines recommend an anti-pneumococcal fluoroquinolone (eg, levofloxacin, moxifloxacin, gemifloxacin) or the
combination of a beta-lactam plus a macrolide (table 6) [2].
● For patients with severe CAP requiring intensive care unit admission, the IDSA/ATS guidelines recommend a beta-lactam (ceftriaxone, cefotaxime, ampicillin-sulbactam) plus either
intravenous azithromycin or an anti-pneumococcal fluoroquinolone unless there is concern for Pseudomonas or methicillin-resistant S. aureus (MRSA) infection. If Pseudomonas is a
concern, an antipseudomonal agent (piperacillin-tazobactam, imipenem, meropenem, or cefepime) PLUS an antipseudomonal fluoroquinolone (ciprofloxacin or high-dose levofloxacin)
should be used. If MRSA is a concern, either vancomycin or linezolid should be added (table 6) [2]. (See 'Intensive care unit' above.)
● The BTS and National Institute for Health and Care Excellence (NICE) guidelines tend to select older antibiotics than those recommended in North America (table 10) [117,120].
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Community-acquired
pneumonia in adults".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level
and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety
of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Community-acquired pneumonia in adults (The Basics)")
● Beyond the Basics topic (see "Patient education: Pneumonia in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Most initial treatment regimens for hospitalized patients with community-acquired pneumonia (CAP) are empiric. A limited number of pathogens are responsible for the majority of cases
(table 1 and table 2) for which a pathogen is known, but in most cases a pathogen is not identified. The most commonly detected bacterial pathogen is Streptococcus pneumoniae. Other
common pathogens include Haemophilus influenzae, the atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella spp), oropharyngeal aerobes and anaerobes
(in the setting of aspiration), and respiratory viruses. (See 'Likely pathogens' above.)
● The approach to diagnostic testing for hospitalized patients with CAP is summarized in the following table (table 4). In addition to the tests recommended in the table, we recommend
testing for a specific organism when, based on clinical or epidemiologic data, pathogens that would not respond to usual empiric therapy are suspected (table 5). (See 'Diagnostic testing'
above.)
● We generally start antibiotic therapy as soon as we are confident that CAP is the appropriate working diagnosis and, ideally, within four hours of presentation for patients being admitted to
the general medical ward. In patients with sepsis or septic shock, antibiotics should be started within one hour of presentation. We favor administration of intravenous (IV) antibiotics at the
start of therapy because of the high mortality associated with CAP and the uncertainty of adequate gastrointestinal absorption or oral antibiotics in severely ill patients. (See 'Antimicrobial
initiation' above.)
● For hospitalized patients not requiring intensive care unit (ICU) admission, we suggest initial combination therapy with an anti-pneumococcal beta-lactam (ceftriaxone, cefotaxime,
ceftaroline, ertapenem, or ampicillin-sulbactam) plus a macrolide (azithromycin or clarithromycin XL) (algorithm 2) (Grade 2C).
For patients who cannot take a beta-lactam plus a macrolide, we suggest monotherapy with a respiratory fluoroquinolone (levofloxacin, moxifloxacin, or gemifloxacin) (Grade 2C).
Coverage for Pseudomonas or drug-resistant pathogens, such as MRSA, should be included in patients with risk factors. Doxycycline may be used as an alternative to a macrolide,
especially in patients at high risk of QT interval prolongation. (See 'Medical ward' above.)
● For hospitalized patients requiring ICU care, we suggest initial combination therapy with an anti-pneumococcal beta-lactam (ceftriaxone, cefotaxime, ceftaroline, ampicillin-sulbactam, or
ertapenem) plus IV therapy with azithromycin (Grade 2C). For patients who cannot take azithromycin, we suggest a respiratory fluoroquinolone (levofloxacin or moxifloxacin) for the
second agent (ie, in combination with a beta-lactam) (Grade 2C).
For patients with MRSA risk factors, we suggest the addition of either vancomycin (15 mg/kg IV every 12 hours, adjusted to a trough level of 15 to 20 mcg/mL and for renal function; in
seriously ill patients, a loading dose of 25 to 30 mg/kg may be given) or linezolid (600 mg IV every 12 hours) (algorithm 3) (Grade 2B).
For patients at risk for Pseudomonas or drug-resistant pathogens, coverage for these pathogens should be included. (See 'Intensive care unit' above.)
● The use of glucocorticoids as adjunctive treatment for CAP is controversial. We consider the potential benefits and risk of adjunctive glucocorticoids in each patient and administer
glucocorticoids when the potential benefits outweigh the potential risks.
For patients with CAP who have evidence of an exaggerated or dysregulated host inflammatory response, defined as sepsis or respiratory failure with an FiO2 requirement of >50 percent
plus one or more of the following features (metabolic acidosis with an arterial pH of <7.3, lactate >4 mmol/L, or a C-reactive protein >150 mg/L), we suggest giving adjunctive
glucocorticoids (Grade 2B). These patients are at high risk of mortality and are likely to benefit. Reasons to avoid glucocorticoids in such patients include risk factors for severe adverse
events such as recent gastrointestinal bleeding, poorly controlled diabetes, or severe immunocompromise. We also avoid glucocorticoids in patients with CAP known to be caused by a
viral pathogen such as influenza or a fungal pathogen such as Aspergillus.
For other hospitalized patients, we make the decision to give adjunctive glucocorticoids on a case-by-case basis but generally find that the potential for harm outweighs the potential for
benefit in patients who are at low risk for mortality. (See 'Adjunctive glucocorticoids' above.)
● Once a pathogen has been established based upon reliable microbiologic methods, we favor narrowing therapy ("de-escalation") to target the specific pathogen in order to avoid antibiotic
overuse. (See 'Narrowing therapy' above.)
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● Patients should be switched from intravenous to oral therapy when they are hemodynamically stable, demonstrate some clinical improvement (in fever, respiratory status, white blood
count), and are able to take oral medications (algorithm 4). (See 'Switching to oral therapy' above.)
● Hospital discharge is appropriate when the patient is clinically stable from the pneumonia, can take oral medication, has no other active medical problems, and has a safe environment for
continued care; patients do not need to be kept overnight for observation following the switch. Patients who have been discharged from the hospital with CAP should have a follow-up visit,
usually within one week. (See 'Duration of hospitalization' above and 'Clinical follow-up after discharge' above.)
● Duration of treatment in patients with CAP who have a good clinical response within the first two to three days of therapy should generally be five to seven days. In addition, we use
procalcitonin to guide the decision to stop antibiotics. We generally obtain a level at the time of diagnosis and repeat the level every two days in patients who are clinically stable. We
determine the need for continued antibiotic therapy based on clinical improvement, serial procalcitonin levels, microbiologic diagnosis, and the presence of complications (algorithm 6).
(See 'Duration of therapy' above.)
● The duration of therapy may need to be extended beyond seven days in certain patients despite clinical stability and low procalcitonin levels. Longer treatment is indicated if the initial
therapy was not active against the subsequently identified pathogen, if extrapulmonary infection is identified (eg, meningitis or endocarditis), or if the patient has documented
Pseudomonas aeruginosa, Staphylococcus aureus, or Legionella pneumonia or pneumonia caused by some less common pathogens (algorithm 5). (See 'Duration of therapy' above.)
● Most patients with clinical resolution after treatment do not require a follow-up chest radiograph. We perform chest radiograph at 7 to 12 weeks following treatment in patients >50 years of
age, particularly in males and smokers in this age group. (See 'Radiographic response' above.)
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Topic 7027 Version 96.0
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GRAPHICS
Community-acquired pneumonia: Determining the appropriate site of treatment in adults
ICU: intensive care unit; ED: emergency department; PSI: Pneumonia Severity Index.
* Although a definitive etiologic diagnosis is often not established until after the site of treatment decision has been made, clinical or epidemiologic evidence favoring a pathogen associated
with rapidly progressive pneumonia (eg, post-influenza bacterial pneumonia, severe acute respiratory syndrome, Middle East respiratory syndrome, avian influenza [eg, H5N1, H7N9],
Legionella pneumonia) should be considered and, if deemed likely, warrant hospital admission.
¶ Among the available scoring systems for determining the need for admission in patients with community-acquired pneumonia (CAP), we prefer the PSI because it the best studied and
validated. If a less complex scoring system is desired, the CURB-65 score is a reasonable alternative, although its effectiveness and safety in guiding the initial site of treatment have not been
empirically assessed. Refer to the UpToDate topic on assessing severity and determining the appropriate site of care in patients with CAP for additional details and to access PSI and CURB-65
calculators.
Δ Scoring systems, such as the PSI and CURB-65, and clinical criteria are intended to supplement rather than override the judgment of the physician. Factors other than the predictors
included in the rules and the clinical criteria may be important when making an admission decision or selecting the site of inpatient care. As examples, patients with early signs of sepsis or
rapidly progressive illness are not well represented by severity scores. Patients with these features may warrant hospitalization and/or ICU admission regardless of score. Conversely, older
age may be overrepresented in severity scores; this should be taken into account when determining site of care.
◊ Using the CURB-65 score, if the patient has a score of 1 because he or she is ≥65 years of age and he or she has no major comorbidities, hospital admission is not necessarily indicated.
§ Some PSI class II and III patients may benefit from in-home health care support, also termed "hospital-at-home" (eg, a visiting nurse, intravenous fluids, intravenous antibiotics).
Graphic 113076 Version 4.0
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Microbial etiology of community-acquired pneumonia*
United States [1] United Kingdom [2] Spain [3] Sweden [4] Asia [5]
Total patients evaluated 2259 323 3524 184 955
Patients in whom a pathogen was 853 (37.8) 280 (86.7) 1463 (41.5) 124 (67.4) ¶ 428 (44.8)
identified
Patients in whom no pathogen was 1406 (62.2) 43 (13.3) 2061 (58.5) 60 (32.6) 527 (55.2)
identified
Pathogen Δ
Bacteria
Streptococcus pneumoniae 115 (5.1) 115 (35.6) 613 (17.4) 70 (38) 114 (11.9)
Klebsiella pneumoniae 0 13 (4.0) 0 0 60 (6.3)
Haemophilus influenzae 13 (0.6) 130 (40.2) 70 (2) 9 (4.9) 59 (6.2)
Pseudomonas aeruginosa 8 (0.3) 9 (2.8) 50 (1.4) 0 26 (2.7)
Staphylococcus aureus 37 (1.6) 33 (10.2) 25 (0.7) 4 (2.2) 19 (2)
Mycobacterium tuberculosis 8 (0.3) 0 2 (1.1) 13 (1.4)
Moraxella catarrhalis 0 44 (13.6) 5 (0.1) 7 (3.8) 12 (1.3)
Mycoplasma pneumoniae 43 (1.9) 6 (1.9) 65 (1.8) ◊ 15 (8.2) ◊ 61/556 (11) ◊
Chlamydia pneumoniae 9 (0.4) 0 50 (1.4) ◊ 0◊ 55/411 (13.4) ◊
Chlamydia psittaci 2 (0.6)
Legionella pneumophila 32 (1.4) 3 (0.9) 118 (3.3) ◊ 3 (1.6) 7/648 (1.1)
Non-pneumophila Legionella spp 3 (0.9)
Coxiella burnetii 0 0 30 (0.8) ◊ 0 0
Gram-negative enteric bacilli 31 (1.4) 37 (11.5) 27 (0.8) 0 0
Acinetobacter baumannii 0 3 (0.9) 0 0 0
Viruses §
Respiratory viruses ¥ 148 (4.2) ◊
Influenza viruses 132 (5.8) 23 (7.1) 14 (7.6) ◊
Rhinovirus 194 (8.6) 41 (12.7) 12 (6.5)
Respiratory syncytial virus 68 (3.0) 4 (1.2) 7 (3.8) ◊
Parainfluenza viruses 67 (3.0) 11 (3.4) 7 (3.8) ◊
Coronaviruses 53 (2.3) 9 (2.8) 4 (2.2)
Human metapneumovirus 88 (3.9) 3 (0.9) 4 (2.2)
Adenovirus 32 (1.4) 7 (2.2) 3 (1.6) ◊
Other pathogen 36 (1.6) 54 (1.5) 5 (2.7) 77 (8)
Polymicrobial (>1 pathogen 115 (5.1) ‡ 208 (5.9) ◊ 46 (25) ◊ 60 (6.3) ◊

identified)
Diagnostic methods Cultures (blood, endotracheal Fast multiplex real-time PCR of lower Cultures (sputum, blood, Cultures (sputum, blood, Cultures (sputum, blood, BAL fluid,
aspirates, quantitative BAL fluid respiratory tract specimens (for S. transthoracic needle aspirate, nasopharyngeal secretions), real- pleural fluid, transthoracic needle
specimens, pleural fluid), PCR from pneumoniae, H. influenzae, M. transbronchial aspirates, BAL fluid, time PCR on sputum (for S. aspiration), serologic testing (for M.
nasopharyngeal and oropharyngeal catarrhalis, S. aureus, E. coli, K. protected specimen brush respiratory pneumoniae, H. influenzae, M. pneumoniae, C. pneumoniae),
swabs (for adenovirus; C. pneumoniae, P. aeruginosa, A. samples, pleural fluid), serologic catarrhalis), PCR from urinary antigen testing (for L.
pneumoniae; coronaviruses 229E, baumannii, M. pneumoniae, C. testing (for M. pneumoniae, C. nasopharyngeal secretions (for M. pneumophila)
HKU1, NL63, and OC43; human pneumoniae, C. psittaci, L. pneumoniae, L. pneumophila, C. pneumoniae), serologic testing (for
metapneumovirus; rhinovirus; pneumophila, non-pneumophila burnetti, influenza A and B, M. pneumoniae, C. pneumoniae,
influenza A and B; M. pneumoniae; Legionella spp, influenza A, influenza parainfluenza viruses 1-3, respiratory influenza A and B, parainfluenza
parainfluenza viruses 1-3; B, RSV, parainfluenza viruses 1-3, syncytial virus, adenovirus), urinary viruses 1-3, respiratory syncytial
respiratory syncytial virus), real-time adenovirus, human coronaviruses antigen testing (for S. pneumoniae virus, adenovirus), urinary antigen
PCR from sputum (for L. [229E, HKU1, NL63, and OC43], or L. pneumophila), testing (for S. pneumoniae, L.
pneumophila), PCR from pleural fluid human metapneumovirus, immunofluorescence assay plus virus pneumophila), virus isolation and
(for Enterobacteriaceae, H. rhinovirus) † isolation or reverse transcriptase PCR real-time PCR (for influenza A and B,
influenzae, Pseudomonas, S. aureus, for influenza A and B, parainfluenza parainfluenza viruses 1-3, respiratory
S. anginosus, S. mitis, S. viruses 1-3, respiratory syncytial syncytial virus, adenovirus, human
pneumoniae, S. pyogenes), urinary virus, adenovirus metapneumovirus, rhinovirus) on
antigen testing (for L. pneumophila nasopharyngeal secretions
and S. pneumoniae), serologic
testing (for adenovirus, human
metapneumovirus, influenza A and B,
parainfluenza viruses, respiratory
syncytial virus)
Site of care Inpatient Inpatient 1302 inpatient, 161 outpatient Inpatient 593 inpatient, 362 outpatient
BAL: bronchoalveolar lavage; PCR: polymerase chain reaction.

* Results are reported as number of patients (percent).
¶ A pathogen was identified in 85 percent of the 38 patients who had all of the diagnostic studies performed, as described in "Diagnostic methods."
Δ Results are reported as the number of patients with a given pathogen, followed by the percentage of patients in whom the pathogen was identified out of all of the patients in the study. For example, in the first column, S. pneumoniae was
detected in 115 of 2259 patients in the study (5.1 percent). Among the 853 patients in whom a pathogen was identified, S. pneumoniae was detected in 13.5 percent.
◊ Pathogens detected by serologic methods may represent recent infection rather than active infection.
§ Viral etiology was not evaluated.
¥ Influenza viruses A or B, parainfluenza viruses 1-3, respiratory syncytial virus, adenovirus.
‡ Some patients had >1 pathogen identified, but the total number was not reported.
† Lower respiratory tract cultures were also sent from patients included in this study, but they are not shown in this table because complete data (ie, total number of patients in whom a pathogen was detected by either molecular methods or by
culture) were not reported in the study.
References:
1. Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 2015; 373:415.
2. Gadsby NJ, Russell CD, McHugh MP, et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis 2016; 62:817.
3. Cillóniz C, Ewig S, Polverino E, et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
4. Johansson N, Kalin M, Tiveljung-Lindell A, et al. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 2010; 50:202.
5. Song JH, Oh WS, Kang CI, et al. Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens. Int J
Antimicrob Agents 2008; 31:107.
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Microbial etiology of community-acquired pneumonia by site of care*
Outpatients Ward patients Intensive care unit patients
Spain [1 ] Canada [2] Spain [1] United States [3] Spain [1] United States [3]
Total patients evaluated 514 507 2521 585 488 145
Patients in whom a pathogen 161 (31.3) 244 (48.1) 1042 (41) 120 (21) 260 (53) 57 (39)
was identified
Patients in whom no pathogen 353 (68.7) 263 (51.9) 1479 (59) 465 (79) 228 (47) 88 (61)
was identified
Pathogen ¶
Streptococcus pneumoniae 56 (10.9) 30 (5.9) 447 (17.7) 38 (6.5) 110 (22.5) 22 (15.2)
Other Streptococcus spp 0 5 (1.0) 0 0 0 0
Haemophilus influenza 8 (1.6) 25 (4.9) 54 (2.1) 16 (2.7) 8 (1.6) 3 (2.1)
Haemophilus parainfluenzae 0 10 (2.0) 0 0 0 0
Moraxella cattarrhalis 0 6 (1.2) 4 (0.2) 0 1 (0.2) 0
Legionella pneumophila 10 (1.9) Δ 87 (3.5) ◊ 21 (4.3) ◊
Mycoplasma pneumoniae 27 (5.3) § 87 (17.2) § 32 (1.3) § ¥ 6 (1.2) § ¥
Chlamydia pneumoniae 10 (1.9) § 72 (14.2) § 32 (1.3) § ¥ 8 (1.6) § ¥
Coxiella burnetii 11 (2.1) § Δ 17 (0.7) § ¥ 2 (0.4) § ¥
Staphylococcus aureus 1 (0.2) 6 (1.2) 18 (0.7) 25 (4.3) 6 (1.2) 12 (8.3)
MSSA 1 (0.2) NR 9 (0.4) 18 (3.1) 4 (0.8) 9 (6.2)
MRSA 0 NR 9 (0.4) 7 (1.2) 2 (0.4) 3 (2.1)
Gram-negative enteric bacilli 1 (0.2) 2 (0.4) 23 (0.9) 15 (2.6) 3 (0.6) 4 (2.8)
Pseudomonas aeruginosa 1 (0.2) 1 (0.2) 37 (1.5) 12 (2.1) 12 (2.5) 8 (5.5)
Respiratory viruses ‡ 15 (2.9) § † 123 (4.9) § † 10 (2.0) § †
Other pathogen 6 (1.2) 14 (2.8) 33 (1.3) 8 (1.4) 15 (3.1) 3 (2.1)
>1 pathogen 15 (2.9) ** 135 (5.4) 6 (1.0) 58 (11.9) 7 (4.8)
Diagnostic methods Cultures (sputum, blood, Cultures (sputum, blood), Cultures (sputum, blood, Cultures (blood, endotracheal Cultures (sputum, blood, Cultures (blood, endotracheal
transthoracic needle aspirate, serologic testing (for M. transthoracic needle aspirate, aspirates, protected specimen transthoracic needle aspirate, aspirates, protected specimen
transbronchial aspirates, BAL pneumoniae, C. pneumoniae) transbronchial aspirates, BAL brush respiratory samples, BAL transbronchial aspirates, BAL brush respiratory samples, BAL
fluid, protected specimen brush fluid, protected specimen brush fluid, pleural fluid), urinary fluid, protected specimen brush fluid, pleural fluid), urinary
respiratory samples, pleural respiratory samples, pleural antigen (for L. pneumophila) respiratory samples, pleural antigen testing (for L.
fluid), serologic testing (for M. fluid), serologic testing (for M. fluid), serologic testing (for M. pneumophila)
pneumoniae, C. pneumoniae, pneumoniae, C. pneumoniae, pneumoniae, C. pneumoniae,
L. pneumophila, C. burnetti, L. pneumophila, C. burnetti, L. pneumophila, C. burnetti,
influenza A and B, influenza A and B, influenza A and B,
parainfluenza viruses 1 to 3, parainfluenza viruses 1 to 3, parainfluenza viruses 1 to 3,
respiratory syncytial virus, respiratory syncytial virus, respiratory syncytial virus,
adenovirus), urinary antigen adenovirus), urinary antigen adenovirus), urinary antigen
testing (for S. pneumoniae and testing (for S. pneumoniae and testing (for S. pneumoniae and
L. pneumophila), L. pneumophila), L. pneumophila),
immunofluorescence assay plus immunofluorescence assay plus immunofluorescence assay plus
virus isolation or reverse virus isolation or reverse virus isolation or reverse
transcriptase PCR for influenza transcriptase PCR for influenza transcriptase PCR for influenza
A and B, parainfluenza viruses A and B, parainfluenza viruses A and B, parainfluenza viruses
1 to 3, respiratory syncytial 1 to 3, respiratory syncytial 1 to 3, respiratory syncytial
virus, adenovirus virus, adenovirus virus, adenovirus
MSSA: methicillin-susceptible Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus; NR: not reported; BAL: bronchoalveolar lavage; PCR: polymerase chain reaction.
* Results are reported as number of patients (percent). Different methods were used for diagnosis in each study, as described in the row on diagnostic methods.
¶ Results are reported as the number of patients with a given pathogen, followed by the percentage of patients in whom the pathogen was identified out of all of the patients in the study. For example, in the first column, S. pneumoniae was
detected in 30 of 507 patients in the study (5.9 percent). Among the 244 patients in whom a pathogen was identified, S. pneumoniae was detected in 12.3 percent.
Δ Testing for Legionella spp and C. burnetti was not performed.
◊ Legionella urinary antigen testing was performed in 35 ward patients and 26 intensive care unit patients, but all results were negative. Legionella culture was not performed.
§ Pathogens detected by serologic methods may represent recent infection rather than active infection.
¥ Testing for M. pneumoniae, C. pneumoniae, and C. burnetii was not performed.
‡ Influenza viruses A or B, parainfluenza viruses 1 to 3, respiratory syncytial virus, adenovirus.
† Testing for viruses was not performed.
** Some patients had >1 pathogen isolated, but the details were not reported.
References:
1. Cillóniz C, Ewig S, Polverino E, et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
2. Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Bnjidic Z. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60.
3. Restrepo MI, Mortensen EM, Velez JA, et al. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133:610.
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Risk factors for CAP caused by MRSA and Pseudomonas
MRSA Pseudomonas
Known MRSA colonization Known Pseudomonas colonization
Detection of gram-positive cocci in clusters on a good-quality sputum Gram stain Detection of gram negative rods on a good-quality sputum Gram stain
Antimicrobial therapy (particularly with a fluoroquinolone) in the prior three months Antimicrobial therapy in the prior three months
Recent influenza-like illness Recent hospitalization or stay in a long-term care facility
Necrotizing or cavitary pneumonia* Frequent COPD exacerbations requiring glucocorticoid and/or antibiotic use
Empyema* Other structural lung diseases (eg, bronchiectasis, cystic fibrosis)
Immunosuppression Immunosuppression
Risk factors for MRSA colonization, including:

End-stage renal disease
Crowded living conditions (eg, incarceration)*
Injection drug use*
Contact sports participation*
Men who have sex with men*
CAP: community-acquired pneumonia; MRSA: methicillin-resistant Staphylococcus aureus; COPD: chronic obstructive pulmonary disease.
* This factor is associated with community-acquired MRSA infection, which can cause severe toxin-mediated infection. Refer to the UpToDate topic on MRSA infections and treatment of CAP in patients with risk factors for MRSA infection for
further detail.
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Clinical indications for diagnostic testing for community-acquired pneumonia*
Pneumococcal
Indication Blood culture Sputum culture Legionella UAT Multiplex PCR ¶ Other
UAT
Intensive care unit admission X X X X X XΔ
Failure of outpatient antibiotic therapy X X X X
Cavitary infiltrates X X X◊
Leukopenia X X X
Active alcohol abuse X X X X X
Chronic severe liver disease X X X
Severe obstructive/structural lung disease X X
Asplenia (anatomic or functional) X X X
Recent travel (within past two weeks) X X X§
Positive Legionella UAT result X¥ NA
Positive pneumococcal UAT result X X NA
Pleural effusion X X X X X‡
UAT: urinary antigen test; PCR: polymerase chain reaction; NA: not applicable.
* During outbreaks, testing for specific pathogens (eg, Middle East respiratory syndrome coronavirus, novel influenza viruses [H7N9 influenza], Legionella, Mycoplasma pneumoniae, Chlamydophila pneumoniae) may be necessary. As an
example, patients presenting with community-acquired pneumonia who have traveled to the Middle East within 14 days before onset of illness should be tested for Middle East respiratory syndrome coronavirus. In patients who have traveled to
or lived in regions that are endemic for tuberculosis, testing for tuberculosis is indicated.
¶ A multiplex PCR assay, the FilmArray Respiratory Panel, that can detect multiple respiratory viruses, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Bordetella pertussis is available. The use of this assay may be limited by cost
and/or availability.
Δ Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage.
◊ Fungal and tuberculosis cultures.
§ Refer to the UpToDate topic and table on the risk factors for CAP pathogens for details.
¥ Selective media for Legionella spp.
‡ Thoracentesis and pleural fluid cultures.
Adapted with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect
Dis 2007; 44:S27. Copyright ©2007 University of Chicago.
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Epidemiologic conditions and/or risk factors related to specific pathogens in community-acquired pneumonia
Condition Commonly encountered pathogen(s)
Alcoholism Streptococcus pneumoniae, oral anaerobes, Klebsiella pneumoniae, Acinetobacter species, Mycobacterium tuberculosis
COPD and/or smoking Haemophilus influenzae, Pseudomonas aeruginosa, Legionella species, S. pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae
Aspiration Gram-negative enteric pathogens, oral anaerobes
Lung abscess CA-MRSA, oral anaerobes, endemic fungal pneumonia, M. tuberculosis, atypical mycobacteria
Exposure to bat or bird droppings Histoplasma capsulatum
Exposure to birds Chlamydia psittaci (if poultry: avian influenza)
Exposure to rabbits Francisella tularensis
Exposure to farm animals or parturient cats Coxiella burnetti (Q fever)
HIV infection (early) S. pneumoniae, H. influenzae, M. tuberculosis
HIV infection (late) The pathogens listed for early infection plus Pneumocystis jirovecii, Cryptococcus, Histoplasma, Aspergillus, atypical mycobacteria (especially Mycobacterium kansasii), P. aeruginosa,
H. influenzae
Hotel or cruise ship stay in previous two weeks Legionella species
Travel to or residence in southwestern United Coccidioides species, hantavirus

States
Travel to or residence in Southeast and East Asia Burkholderia pseudomallei, avian (H5N1, H7N9) influenza, SARS coronavirus
Travel to or residence in the Arabian peninsula Middle East respiratory syndrome coronavirus
Influenza active in community Influenza, S. pneumoniae, Staphylococcus aureus, H. influenzae
Cough >2 weeks with whoop or posttussive Bordetella pertussis

vomiting
Structural lung disease (eg, bronchiectasis) Pseudomonas aeruginosa, Burkholderia cepacia, S. aureus
Injection drug use S. aureus, anaerobes, M. tuberculosis, S. pneumoniae
Endobronchial obstruction Anaerobes, S. pneumoniae, H. influenzae, S. aureus
In context of bioterrorism Bacillus anthracis (anthrax), Yersinia pestis (plague), Francisella tularensis (tularemia)
COPD: chronic obstructive pulmonary disease; CA-MRSA: community-acquired methicillin-resistant Staphylococcus aureus; HIV: human immunodeficiency virus; SARS: severe acute respiratory syndrome.
Adapted with permission from: Mandell, LA, Wunderink, RG, Anzueto, A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect
Dis 2007; 44:S27. Copyright © 2007 University of Chicago Press.
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IDSA/ATS guidelines: Recommended empiric antibiotics for community-acquired pneumonia in adults
Outpatient treatment
1. Previously healthy and no use of antimicrobials within the previous three months:
A macrolide (az ithromycin, clarithromycin, or erythromycin)

OR
Doxycyline*
2. Presence of comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; or use of antimicrobials within
the previous three months (in which case an alternative from a different class should be selected):
A respiratory fluoroquinolone (moxifloxacin, gemifloxacin ¶, or levofloxacin [750 mg])

OR
A beta-lactam (first-line agents: high-dose amoxicillin, amoxicillin-clavulanate; alternative agents: ceftriaxone, cefpodoxime, or cefuroxime) PLUS a macrolide (azithromycin, clarithromycin, or erythromycin)*
3. In regions with a high rate (>25 percent) of infection with high-level (MIC ≥16 mcg/mL) macrolide-resistant Streptococcus pneumoniae, consider use of alternative agents listed in (2) above.
Inpatients, non-ICU treatment

A respiratory fluoroquinolone (moxifloxacin, gemifloxacin ¶ , or levofloxacin [750 mg])
OR
An antipneumococcal beta-lactam (preferred agents: cefotaxime, ceftriaxone, or ampicillin-sulbactam; or ertapenem for selected patients) Δ PLUS a macrolide (azithromycin, clarithromycin, or erythromycin)* ◊
Inpatients, ICU treatment

An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS azithromycin
OR
An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS a respiratory fluoroquinolone (moxifloxacin, gemifloxacin ¶, or levofloxacin [750 mg])
OR
For penicillin-allergic patients, a respiratory fluoroquinolone (moxifloxacin, gemifloxacin ¶, or levofloxacin [750 mg]) PLUS aztreonam
Special concerns
If Pseudomonas aeruginosa is a consideration:
An antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS either ciprofloxacin or levofloxacin (750 mg)
OR
The above beta-lactam PLUS an aminoglycoside PLUS azithromycin
OR
The above beta-lactam PLUS an aminoglycoside PLUS a respiratory fluoroquinolone (moxifloxacin, gemifloxacin ¶, or levofloxacin [750 mg]); for penicillin-allergic patients, substitute aztreonam for above beta-lactam
If CA-MRSA is a consideration:
Add vancomycin or linezolid
This table provides the 2007 recommendations of the Infectious Diseases Society of America and the American Thoracic Society for reference purposes. Refer to the UpToDate text for information about choosing between the
different guidelines and about the preferred doses and durations of the individual antibiotics.
IDSA: Infectious Diseases Society of America; ATS: American Thoracic Society; CAP: community-acquired pneumonia; CA-MRSA: community-acquired methicillin-resistant Staphylococcus aureus; ICU: intensive care unit; MIC: minimum
inhibitory concentration.
* Doxycycline may be used as an alternative to a macrolide, but there is stronger evidence to support the use of a macrolide than doxycycline for CAP.
¶ Gemifloxacin has been removed from the United States market but may remain available elsewhere.
Δ Ceftaroline can be used as an alternative to these agents. It is a fifth-generation cephalosporin that was not included in the 2007 IDSA/ATS guidelines for the management of CAP since it was not US Food and Drug Administration (FDA)
approved for CAP until 2010. Ceftaroline has a spectrum of activity like that of ceftriaxone, including good in vivo activity against Streptococcus pneumoniae. It is also active against MRSA, unlike older cephalosporins. However, it is not FDA
approved for CAP involving MRSA since patients with MRSA were excluded from the trials. Ceftaroline is more expensive (average wholesale price 82 USD per day) compared with the alternative agents, which are all off patent. [1]
◊ Monotherapy with tigecycline may be used in patients who cannot take either a beta-lactam or a fluoroquinolone. Tigecycline was not included in the 2007 IDSA/ATS guidelines for the management of CAP because it was not FDA approved for
CAP until 2009. It has been associated with increased mortality, as discussed further in the UpToDate topic review.
Reference:
1. File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-
acquired pneumonia. Clin Infect Dis 2010; 51:1395.
Modified with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect
Dis 2007; 44 Suppl 2:S27. Copyright © 2007 University of Chicago Press. http://www.journals.uchicago.edu/.
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Community-acquired pneumonia: Empiric antibiotic selection for adults admitted to the general medical ward*
MRSA: methicillin-resistant Staphylococcus aureus; COPD: chronic obstructive pulmonary disease.

* This algorithm is intended for patients in whom admission to a general medical ward is considered appropriate. Refer to related UpToDate content to determine the site of care. Antibiotics should be administered as soon as possible after
diagnosing community-acquired pneumonia (CAP). If the etiology of CAP has been identified based upon reliable microbiologic methods and there is no laboratory or epidemiologic evidence of coinfection, treatment regimens should be simplified
and directed to that pathogen.
¶ Individuals with a past reaction to penicillin that was mild (not Stevens Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms [DRESS]) and did not have features of an IgE-mediated reaction
can receive a broad-spectrum (third- or fourth-generation) cephalosporin or carbapenem safely.
Δ Empiric therapy with aztreonam plus levofloxacin plus an aminoglycoside is generally appropriate for patients who warrant antipseudomonal coverage but have beta-lactam allergies that preclude the use of penicillins, cephalosporins, and
carbapenems. However, patients with a prior life-threatening or anaphylactic reaction to ceftazidime should not be given aztreonam unless evaluated by an allergy specialist because of the possibility of cross-reactivity. Such patients can receive
levofloxacin plus an aminoglycoside for antipseudomonal coverage in the interim.
◊ Combination therapy with a beta-lactam plus a macrolide and monotherapy with a respiratory fluoroquinolone are of generally comparable efficacy for CAP overall. However, many observational studies have suggested that beta-lactam plus
macrolide combination regimens are associated with better clinical outcomes in patients with severe CAP, possibly due to the immunomodulatory effects of macrolides. Furthermore, the severity of adverse effects (including the risk for
Clostridioides [formerly Clostridium] difficile infection) and the risk of selection for resistance in colonizing organisms are generally thought to be greater with fluoroquinolones than with the combination therapy regimens. For both of these
reasons, we generally prefer combination therapy with a beta-lactam plus a macrolide rather than monotherapy with a fluoroquinolone. Nevertheless, cephalosporins and other antibiotic classes also increase the risk of C. difficile infection. Recent
antibiotic use should also inform the decision about the most appropriate regimen; if the patient has used a beta-lactam in the prior three months, a fluoroquinolone should be chosen, if possible, and vice versa.
§ The combination of vancomycin and piperacillin-tazobactam has been associated with acute kidney injury. In patients who require an anti-MRSA agent and an antipseudomonal/antipneumococcal beta-lactam, options include using a beta-lactam
other than piperacillin-tazobactam (eg, cefepime or ceftazidime) or, if piperacillin-tazobactam is favored, using linezolid instead of vancomycin.
¥ Examples of contraindications include increased risk for a prolonged QT interval and allergy.
‡ Doxycycline should not be used in pregnant women.
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Community-acquired pneumonia: Empiric antibiotic selection for adults admitted to the intensive care unit*
MRSA: methicillin-resistant Staphylococcus aureus; COPD: chronic obstructive pulmonary disease.

* This algorithm is intended for patients in whom admission to an intensive care unit is considered appropriate. Refer to related UpToDate content to determine the site of care. Antibiotics should be administered as soon as possible after
diagnosing community-acquired pneumonia (CAP). If the etiology of CAP has been identified based upon reliable microbiologic methods and there is no laboratory or epidemiologic evidence of coinfection, treatment regimens should be simplified
and directed to that pathogen.
¶ Individuals with a past reaction to penicillin that was mild (not Stevens Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms [DRESS]) and did not have features of an IgE-mediated reaction
can receive a broad-spectrum (third- or fourth-generation) cephalosporin or carbapenem safely.
Δ Empiric therapy with aztreonam plus levofloxacin plus an aminoglycoside is generally appropriate for patients who warrant antipseudomonal coverage but have beta-lactam allergies that preclude the use of penicillins, cephalosporins, and
carbapenems. However, patients with a prior life-threatening or anaphylactic reaction to ceftazidime should not be given aztreonam unless evaluated by an allergy specialist because of the possibility of cross-reactivity. Such patients can receive
levofloxacin plus an aminoglycoside for antipseudomonal coverage in the interim.
◊ Regimens containing either a macrolide or fluoroquinolone have been generally comparable in clinical trials. However, many observational studies have suggested that macrolide-containing regimens are associated with better clinical outcomes
for patients with severe CAP, possibly due to the immunomodulatory effects of macrolides. Furthermore, the severity of adverse effects (including the risk for Clostridioides [formerly Clostridium] difficile infection) and the risk of selection for
resistance in colonizing organisms are generally thought to be greater with fluoroquinolones than with other antibiotic classes. For this reason, we generally favor a macrolide-containing regimen in this setting, unless there is a specific reason to
avoid macrolides, such as patient allergy or intolerance. Recent antibiotic use should also inform the decision about the most appropriate regimen; if the patient has used a beta-lactam in the prior three months, a fluoroquinolone should be
chosen, if possible, and vice versa.
§ The combination of vancomycin and piperacillin-tazobactam has been associated with acute kidney injury. In patients who require an anti-MRSA agent and an antipseudomonal/antipneumococcal beta-lactam, options include using a beta-
lactam other than piperacillin-tazobactam (eg, cefepime or ceftazidime) or, if piperacillin-tazobactam is favored, using linezolid instead of vancomycin.
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Usual duration of findings in treated community-acquired pneumonia
Abnormality Duration (days)
Tachycardia and hypotension 2
Fever, tachypnea, and hypoxia 3
Cough 14
Fatigue 14
Infiltrates on chest radiograph 30
References:
1. Marrie TJ, Beecroft MD, Herman-Gnjidic Z. Resolution of symptoms in patients with community-acquired pneumonia treated on an ambulatory basis. J Infect 2004; 49:302.
2. Metlay JP, Atlas SJ, Borowsky LH, Singer DE. Time course of symptom resolution in patients with community-acquired pneumonia. Respir Med 1998; 92:1137.
3. Fine MJ, Stone RA, Singer DE, et al. Processes and outcomes of care for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study. Arch Intern Med 1999; 159:970.
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Recommended antimicrobial therapy for specific pathogens causing community-acquired pneumonia in adults
Organism Preferred antimicrobial(s) Alternative antimicrobial(s)
Streptococcus pneumoniae
Penicillin nonresistant; MIC <2 microgram/mL Penicillin G, amoxicillin Macrolide, cephalosporins (oral [cefpodoxime, cefprozil, cefuroxime, cefdinir,
cefditoren] or parenteral [cefuroxime, ceftriaxone, cefotaxime]), clindamycin,
doxycyline, respiratory fluoroquinolone*
Penicillin resistant; MIC ≥2 microgram/mL Agents chosen on the basis of susceptibility, including cefotaxime, ceftriaxone, Vancomycin, linez olid, high-dose amoxicillin (3 g/day with penicillin MIC ≤4
fluoroquinolone microgram/mL)
Haemophilus influenzae
Non-beta-lactamase producing Amoxicillin Fluoroquinolone, doxycycline, azithromycin, clarithromycin ¶
Beta-lactamase producing Second- or third-generation cephalosporin, amoxicillin-clavulanate Fluoroquinolone, doxycycline, azithromycin, clarithromycin ¶
Mycoplasma pneumoniae/Chlamydophila pneumoniae Macrolide, a tetracycline Fluoroquinolone
Legionella species Fluoroquinolone, azithromycin Doxycyline
Chlamydophila psittaci A tetracycline Macrolide
Coxiella burnetii A tetracycline Macrolide
Francisella tularensis Doxycycline Gentamicin, streptomycin
Yersinia pestis Streptomycin, gentamicin Doxycyline, fluoroquinolone
Bacillus anthracis (inhalation) Ciprofloxacin, levofloxacin, doxycycline (usually with second agent) Other fluoroquinolones; beta-lactam, if susceptible; rifampin; clindamycin;
chloramphenicol
Enterobacteriaceae Third-generation cephalosporin, carbapenem Δ (drug of choice if extended- Beta-lactam/beta-lactamase inhibitor ◊, fluoroquinolone
spectrum beta-lactamase producer)
Pseudomonas aeruginosa Antipseudomonal beta-lactam § plus (ciprofloxacin or levofloxacin ¥ or Aminoglycoside plus (ciprofloxacin or levofloxacin ¥ )
aminoglycoside)
Burkholderia pseudomallei Carbapenem, ceftazidime Fluoroquinolone, TMP-SMX
Acinetobacter species Carbapenem Cephalosporin-aminoglycoside, ampicillin-sulbactam, colistin
Staphylococcus aureus
Methicillin susceptible Antistaphylococcal penicillin ‡ Cefazolin, clindamycin
Methicillin resistant Vancomycin or linezolid TMP-SMX
Bordetella pertussis Macrolide TMP-SMX
Anaerobe (aspiration) Beta-lactam/beta-lactamase inhibitor ◊, clindamycin Carbapenem
Influenza virus Refer to associated topic reviews †
Mycobacterium tuberculosis Isoniazid plus rifampin plus ethambutol plus pyrazinamide Depends on susceptibility pattern. Refer to associated topic reviews.
Coccidioides species For uncomplicated infection in a normal host, no therapy generally Amphotericin B
recommended; for therapy, itraconazole, fluconazole.
Histoplasmosis Itraconazole** Amphotericin B**
Blastomycosis Itraconazole** Amphotericin B**
Choices should be modified on the basis of susceptibility test results and advice from local specialists. Refer to local references for appropriate doses.
Preferred agent may change over time due to changing resistance patterns and depends on many factors, including severity of illness. Refer to associated UpToDate topic reviews for updated and detailed treatment
recommendations for each pathogen.
MIC: minimum inhibitory concentration; ATS: American Thoracic Society; CDC: United States Centers for Disease Control and Prevention; IDSA: Infectious Diseases Society of America; TMP-SMX: trimethoprim-sulfamethoxazole.
* Levofloxacin, moxifloxacin, gemifloxacin (not a first-line choice for penicillin susceptible strains); ciprofloxacin is appropriate for Legionella and most gram-negative bacilli (including H. influenzae).
¶ Azithromycin is more active in vitro than clarithromycin for H. influenzae.
Δ Imipenem-cilastatin, meropenem, ertapenem.
◊ Piperacillin-tazobactam for gram-negative bacilli, ticarcillin-clavulanate, ampicillin-sulbactam, or amoxicillin-clavulanate.
§ Ticarcillin, piperacillin, ceftazidime, cefepime, aztreonam, imipenem, meropenem.
¥ 750 mg daily.
‡ Nafcillin, oxacillin, flucloxacillin.
† Choice of antiviral regimen depends on type of influenza virus and expected resistance pattern. (Refer to the UpToDate topic on antiviral drugs for the treatment of influenza in adults.)
** Preferred agent depends on severity of illness. Refer to associated UpToDate topic reviews for full discussions.
Adapted with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thorac Society Consensus Guidelines on the Management of Community-acquired Pneumonia in Adults. Clin Infect
Dis 2007; 44:S27. Copyright © 2007 University of Chicago Press.
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Transitioning inpatients with community-acquired pneumonia from IV to

oral antibiotics
(A) Patients should show some clinical response before switching to oral medications. Fever may persist
with lobar pneumonia. Cough from pneumococcal pneumonia may not clear for a week; abnormal chest
radiograph findings usually clear within 4 weeks but may persist for 12 weeks in older individuals and
those with underlying pulmonary disease.
(B) Risk factors for drug-resistant Streptococcus pneumoniae are:
Age >65 years
Beta-lactam, macrolide, or fluoroquinolone therapy within the past three to six months
Alcoholism
Medical comorbidities
Immunosuppressive illness or therapy
Exposure to a child in a daycare center
* Generally avoid in patients with known QT interval prolongation or risk factors for QT interval prolongation.
¶ Dose adjustment is necessary in patients with renal insufficiency.
Δ If the patient has already received 1.5 g of azithromycin, atypical coverage can be discontinued.
25 of 30 27/03/2019 11:49
Duration of antibiotics for community-acquired pneumonia in

inpatients
26 of 30 27/03/2019 11:49
Algorithm for procalcitonin-guided antibiotic discontinuation in clinically stable adult patients with
known or suspected community-acquired pneumonia (CAP)*
* Procalcitonin has not been well studied in immunocompromised patients, trauma or surgery patients, pregnant women, patients with cystic fibrosis,
and patients with chronic kidney disease. The algorithm may not be applicable to these populations or other patients with complex comorbidities.
¶ Optimal thresholds have not been precisely determined. Some experts use a lower threshold, typically 0.1 ng/mL when deciding to discontinue
antibiotics.
Δ Decisions to stop antibiotics should be made in combination with clinical judgment and presume that the patient is stable and that a bacterial
infection that requires a longer course of therapy, such as CAP complicated by bacteremia, was not identified.
◊ Systemic inflammation due to other causes, such as burns, trauma, surgery, pancreatitis, malaria, or invasive candidiasis can also lead to elevated
procalcitonin levels.
§ Reaching a procalcitonin level of <0.25 ng/mL is not a requirement for antibiotic discontinuation. For patients with clinically resolved pneumonia and
levels >0.25 ng/mL, clinical judgment alone is adequate.
27 of 30 27/03/2019 11:49
UpToDate recommendations* for the administration of pneumococcal vaccines (PCV13 and PPSV23) in adults in the United States
PCV13¶ PPSV23
Risk group Underlying condition
Recommended Recommended Revaccination
Immunocompetent persons Chronic heart disease Δ X
Chronic lung disease ◊ X
Diabetes mellitus X
Cerebrospinal fluid leak X X
Cochlear implant X X
Alcoholism X
Chronic liver disease, cirrhosis X
Cigarette smoking X
Age ≥65 X X §
Persons with functional or anatomic Sickle cell disease/other hemoglobinopathy X X X¥

asplenia
Congenital or acquired asplenia X X X¥
Immunocompromised persons Congenital or acquired immunodeficiency ‡ X X X†
Human immunodeficiency virus infection X X X†
Chronic renal failure X X X†
Nephrotic syndrome X X X†
Leukemia X X X†
Lymphoma X X X†
Hodgkin disease X X X†
Generalized malignancy X X X†
Iatrogenic immunosuppression** X X X†
Solid organ transplant X X X†
Multiple myeloma X X X†
PCV13: 13-valent pneumococcal conjugate vaccine (Prevnar 13); PPSV23: 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23).
* For certain recommendations, UpToDate's recommendations differ from those of the United States Advisory Committee on Immunization Practices (ACIP) as outlined in subsequent footnotes.
¶ For those with an indication for PCV13, only one dose is indicated during adulthood.
Δ Including congestive heart failure and cardiomyopathies, excluding hypertension.
◊ Including chronic obstructive pulmonary disease, emphysema, and asthma.
§ The ACIP recommends that all adults aged ≥65 years receive a dose of PPSV23 even if they were vaccinated when they were less than 65 years of age; however, a minimum interval of five years between PPSV23 doses should be maintained.
UpToDate authors agree with the ACIP's recommendation for revaccination with PPSV23 at or after age 65 years; however, following this dose (and in contrast with the ACIP), UpToDate authors also favor revaccinating with PPSV23 at 10-year
intervals because immunologic responses wane in older adult patients. A caveat is that insurance companies may not provide coverage for these subsequent doses. The ACIP recommends that those who are receiving PPSV23 for the first time
at or after age 65 should receive only a single dose (and do not require revaccination).
¥ For patients with anatomic or functional asplenia, UpToDate authors recommend revaccination with PPSV23 every five years. By contrast, the ACIP recommends that patients <65 years of age who have functional or anatomic asplenia be
revaccinated one time five years after the initial dose and again at or after age 65 (and at least five years after the previous dose).
‡ Includes B- (humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease).
† Patients <65 years of age who are immunocompromised should be revaccinated with PPSV23 one time five years after the initial dose and again at or after age 65 (and at least five years after the previous dose). Refer to footnote § above for
additional recommendations for individuals ≥65 years of age.
** Treatment with any immunosuppressive drugs (including long-term glucocorticoids) or radiation therapy.
References:
1. Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014; 63:822.
2. Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012; 61:816.
3. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal
polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep 2010; 59:1102.
28 of 30 27/03/2019 11:49
British Thoracic Society guidelines: Initial empirical treatment regimens for community-acquired pneumonia in adults
Pneumonia severity (based on clinical judgement

Treatment site Preferred treatment Alternative treatment
supported by CURB65 severity score)
Low severity (eg, CURB65 = 0 to 1 or CRB65 score = 0, <3 Home Amoxicillin 500 mg orally three times daily Doxycycline 200 mg loading dose then 100 mg orally once daily or
percent mortality) clarithromycin 500 mg orally twice daily
Low severity (eg, CURB65 = 0 to 1, <3 percent mortality) but Hospital Amoxicillin 500 mg orally three times daily Doxycycline 200 mg loading dose then 100 mg orally once daily or
admission indicated for reasons other than pneumonia severity (eg, If oral administration not possible: amoxicillin 500 mg IV three times clarithromycin 500 mg orally twice daily
social reasons/unstable comorbid illness) daily*
Moderate severity (eg, CURB65 = 2, 9 percent mortality) Hospital Amoxicillin 500 mg to 1 gram orally three times daily plus Doxycycline 200 mg loading dose then 100 mg orally or levofloxacin
clarithromycin 500 mg orally twice daily 500 mg orally once daily or moxifloxacin 400 mg orally once daily ¶
If oral administration not possible: amoxicillin 500 mg IV three times
daily* or benzylpenicillin (penicillin G) 1.2 grams IV four times daily
plus clarithromycin 500 mg IV twice daily*
High severity (eg, CURB65 = 3 to 5, 15 to 40 percent mortality) Hospital (consider Antibiotics given as soon as possible Benzylpenicillin (penicillin G) 1.2 grams IV four times daily plus
critical care review) Co-amoxiclav (amoxicillin-clavulanate potassium) 1.2 grams IV three either levofloxacin 500 mg IV twice daily or ciprofloxacin 400 mg IV
times daily* plus clarithromycin 500 mg IV twice daily* twice daily
(If Legionella strongly suspected, consider adding levofloxacin Δ) OR

Cefuroxime 1.5 grams IV three times daily or cefotaxime 1 gram IV
three times daily or ceftriaxone 2 grams IV once daily, plus
clarithromycin 500 mg IV twice daily*
(If Legionella strongly suspected, consider adding levofloxacin Δ)
This table provides the 2009 guideline recommendations of the British Thoracic Society for reference purposes. Refer to the UpToDate text for information about choosing between the different guidelines and about the preferred
doses and durations of the individual antibiotics.
CAP: community-acquired pneumonia; IV: intravenous.

* Intravenous preparation not available in the United States.
¶ Following reports of an increased risk of adverse hepatic reactions associated with oral moxifloxacin, in October 2008 the European Medicines Agency (EMEA) recommended that moxifloxacin "should be used only when it is considered
inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection."
Δ Caution: Risk of QT prolongation with macrolide-quinolone combination.
Reproduced with permission from: Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64 Suppl 3:iii1. Copyright © 2009 BMJ Publishing Group
Ltd.
29 of 30 27/03/2019 11:49
Contributor Disclosures
Thomas M File, Jr, MD Consultant/Advisory Boards: Merck [HAI (Imipenem-relebactam)]; MotifBio [Gram-positive infections (Iclaprim)]; Nabriva [Community-acquired pneumonia (Lefamulin)]; Paratek
[Pneumonia; skin infections (Omadacycline)]; Shionogi [HAI (Cefiderocol)]. John G Bartlett, MD Nothing to disclose Julio A Ramirez, MD, FACP Grant/Research/Clinical Trial Support: Pfizer [Vaccines (PCV-13)].
Speaker's Bureau: Pfizer [Vaccines (PCV-13)]; Medicines Company [Respiratory Infections (Meropenen-vaborbactam)]; Amgen [Infections in Immunocompromised hosts (Etanercept)]. Consultant/Advisory Boards:
Pfizer [Vaccines (PCV-13)]; Nabriva [Respiratory Infections (Legamulin)]; Medicines Company [Respiratory Infections (Meropenen-vaborbactam)]; Paratek [Respiratory Infections (Omadacycline)]; Achaogen
[Respiratory Infections (Plazomicin)]; Curetis [Diagnostic tests for Respiratory Infections (Unyvero)]. Sheila Bond, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
30 of 30 27/03/2019 11:49

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Treatment of community-acquired pneumonia in adults who require hospi... https://www.uptodate.com/contents/treatment-of-community-acquired-p...

Official reprint from UpToDate®

Treatment of community-acquired pneumonia in adults who require hospitalization

● (See "Diagnostic approach to community-acquired pneumonia in adults".)

MANAGEMENT OF HEALTH CARE-ASSOCIATED PNEUMONIA

DETERMINING THE APPROPRIATE SITE OF CARE

Risk factors for Pseudomonas or drug-resistant pathogens

Streptococcus pneumoniae — Risk factors for drug-resistant S. pneumoniae in adults include:

● Age >65 years

INITIAL EMPIRIC THERAPY

● The most likely pathogen(s) (see 'Likely pathogens' above)

● Clinical trials proving efficacy

Two of the larger studies showed the following findings:

● Piperacillin-tazobactam (4.5 g every six hours) or

● Imipenem (500 mg IV every six hours) or

● Meropenem (1 g every eight hours) or

● Cefepime (2 g every eight hours) or

● Ciprofloxacin (400 mg every eight hours) or

● Levofloxacin (750 mg daily)

● Delayed radiographic resolution was independently associated with multilobar disease.

Patients who respond to therapy

• Azithromycin – 500 mg once daily

• Clarithromycin – 500 mg twice daily

• Clarithromycin XL – Two 500 mg tablets (1000 mg) once daily

• Doxycycline – 100 mg twice daily

The duration of therapy is discussed below. (See 'Duration of therapy' below.)

● If extrapulmonary infection is identified (eg, meningitis or endocarditis)

● If the patient has necrotizing pneumonia, empyema, or lung abscess [81]

NEW ANTIMICROBIAL AGENTS

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

1. File TM. Community-acquired pneumonia. Lancet 2003; 362:1991.

5. Prina E, Ranzani OT, Torres A. Community-acquired pneumonia. Lancet 2015; 386:1097.

Topic 7027 Version 96.0

Community-acquired pneumonia: Determining the appropriate site of treatment in adults

Graphic 113076 Version 4.0

Microbial etiology of community-acquired pneumonia*

Total patients evaluated 2259 323 3524 184 955

Klebsiella pneumoniae 0 13 (4.0) 0 0 60 (6.3)

Haemophilus influenzae 13 (0.6) 130 (40.2) 70 (2) 9 (4.9) 59 (6.2)

Pseudomonas aeruginosa 8 (0.3) 9 (2.8) 50 (1.4) 0 26 (2.7)

Staphylococcus aureus 37 (1.6) 33 (10.2) 25 (0.7) 4 (2.2) 19 (2)

Mycobacterium tuberculosis 8 (0.3) 0 2 (1.1) 13 (1.4)

Moraxella catarrhalis 0 44 (13.6) 5 (0.1) 7 (3.8) 12 (1.3)

Mycoplasma pneumoniae 43 (1.9) 6 (1.9) 65 (1.8) ◊ 15 (8.2) ◊ 61/556 (11) ◊

Chlamydia pneumoniae 9 (0.4) 0 50 (1.4) ◊ 0◊ 55/411 (13.4) ◊

Chlamydia psittaci 2 (0.6)

Legionella pneumophila 32 (1.4) 3 (0.9) 118 (3.3) ◊ 3 (1.6) 7/648 (1.1)

Non-pneumophila Legionella spp 3 (0.9)

Coxiella burnetii 0 0 30 (0.8) ◊ 0 0

Gram-negative enteric bacilli 31 (1.4) 37 (11.5) 27 (0.8) 0 0

Acinetobacter baumannii 0 3 (0.9) 0 0 0

Respiratory viruses ¥ 148 (4.2) ◊

Influenza viruses 132 (5.8) 23 (7.1) 14 (7.6) ◊

Rhinovirus 194 (8.6) 41 (12.7) 12 (6.5)

Respiratory syncytial virus 68 (3.0) 4 (1.2) 7 (3.8) ◊

Parainfluenza viruses 67 (3.0) 11 (3.4) 7 (3.8) ◊

Coronaviruses 53 (2.3) 9 (2.8) 4 (2.2)

Human metapneumovirus 88 (3.9) 3 (0.9) 4 (2.2)

Adenovirus 32 (1.4) 7 (2.2) 3 (1.6) ◊

Other pathogen 36 (1.6) 54 (1.5) 5 (2.7) 77 (8)